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-ß1-induced the EMT process in vitro. 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/ß-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/ß-catenin pathway and the EMT process, which indicated that it might function as an exploitable treatment target for GCA patients.

The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Transverse versus longitudinal mucosal incision during POEM for esophageal motility disorders: a randomized trial.

BACKGROUND: Longitudinal incision is the commonly used incision for entry into the submucosal space during peroral endoscopic myotomy (POEM) for esophageal motility disorders. Transverse incision is another alternative for entry and retrospective data suggest it has less operative time and chance of gas-related events. METHODS: This was a single-center, randomized trial conducted at a tertiary care hospital. Patients undergoing POEM for esophageal motility disorders were randomized into group A (longitudinal incision) and group B (transverse incision). The primary objective was to compare the time needed for entry into the submucosal space. The secondary objectives were to compare the time needed to close the incision, number of clips required to close the incision, and development of gas-related events. The sample size was calculated as for a non-inferiority design using Kelsey method. RESULTS: Sixty patients were randomized (30 in each group). On comparing the 2 types of incisions, there was no difference in entry time [3 (2, 5) vs 2 (1.75, 5) min, p = 0.399], closure time [7 (4, 13.5) vs 9 (6.75, 19) min, p = 0.155], and number of clips needed for closure [4 (4, 6) vs 5 (4, 7), p = 0.156]. Additionally, the gas-related events were comparable between the 2 groups (capnoperitoneum needing aspiration-5 vs 2, p = 0.228, and development of subcutaneous emphysema-3 vs 1, p = 0.301). CONCLUSION: This randomized trial shows comparable entry time, closure time, number of clips needed to close the incision, and gas-related events between longitudinal and transverse incisions. REGISTRATION NUMBER: CTRI/2021/08/035829.

A novel method of cardia visualization and comfort level enhancement during magnetic capsule gastroscopy via sugar-glued tether-assisted technique: a randomized pilot study inspired by a Chinese snack-making process (with video).

BACKGROUND: Magnetic capsule gastroscopy (MCG) is a non-invasive diagnostic method for the digestive tract. However, its efficiency in visualizing the gastric cardia is often compromised due to the capsule's rapid passage. This study introduces a novel sugar-glued tether-assisted technique inspired by a traditional Chinese snack-making process to enhance cardia visualization and patient comfort during MCG. METHODS: This pilot, open-label, single-center, randomized controlled, non-inferiority study was conducted at Binzhou Medical University Hospital. Seventy-eight patients were enrolled and divided into three groups: conventional MCG, suction cup tether-assisted MCG, and sugar-glued tether-assisted MCG. The primary outcomes included safety, comfort level, and gastric cardia visualization quality. Secondary outcomes assessed technique-associated performance and clinical factors. RESULTS: The sugar-glued tether-assisted MCG demonstrated comparable cardia visualization quality to the suction cup method, with significantly better results than conventional MCG. Comfort levels were significantly higher in the sugar-glued group compared to the suction cup group. The number of swallow attempts was significantly lower in the sugar-glued group, with no adverse events reported. Secondary outcomes showed no significant differences in MCG assembly time and ingestion-to-detachment period between the suction cup and sugar-glued groups. CONCLUSION: The sugar-glued tether-assisted MCG is a feasible and safe modification that enhances gastric cardia visualization while improving patient comfort. This technique provides a cost-effective alternative to the suction cup method, warranting further investigation in larger, multi-center studies.

Long-term outcomes of laparoscopic Heller's myotomy with angle of His accentuation in patients of achalasia cardia.

BACKGROUND: Laparoscopic Heller's myotomy (LHM) is an established treatment for achalasia cardia. Anti-reflux procedures (ARP) are recommended with LHM to reduce the post-operative reflux though the optimal anti-reflux procedure is still debatable. This study reports on the long-term outcomes of LHM with Angle-of-His accentuation (AOH) in patients of achalasia cardia. METHODS: One hundred thirty-six patients of achalasia cardia undergoing LHM with AOH between January 2010 to October 2021 with a minimum follow-up of one year were evaluated for symptomatic outcomes using Eckardt score (ES), DeMeester heartburn (DMH) score and achalasia disease specific quality of life (A-DsQoL) questionnaire. Upper gastrointestinal endoscopy, high resolution manometry (HRM) and timed barium esophagogram (TBE) were performed when feasible and rates of esophagitis and improvement in HRM and TBE parameters evaluated. Time dependent rates of success were calculated with respect to improvement in ES and dysphagia-, regurgitation- and heartburn-free survival using Kaplan-Meier analysis. RESULTS: At a median follow-up of 65.5 months, the overall success (ES ≤ 3) was 94.1%. There was statistically significant improvement in ES, heartburn score and A-DsQoL score (p < 0.00001, p = 0.002 and p < 0.00001). Significant heartburn (score ≥ 2) was seen in 12.5% subjects with 9.5% patients reporting frequent PPI use (> 3 days per week). LA-B and above esophagitis was seen in 12.7%. HRM and TBE parameters also showed a significant improvement as compared to pre-operative values (IRP: p < 0.0001, column height: p < 0.0001, column width: p = 0.0002). Kaplan-Meier analysis showed dysphagia, regurgitation, and heartburn free survival of 75%, 96.2% and 72.3% respectively at 10 years. CONCLUSIONS: LHM with AOH gives a lasting relief of symptoms in patients of achalasia cardia with heartburn rates similar to that reported in studies using Dor's or Toupet's fundoplication with LHM. Hence, LHM with AOH may be a preferred choice in patients of achalasia cardia given the simplicity of the procedure.

Identifying the optimal treatment strategy in patients with resectable non-cardia gastric cancer.

BACKGROUND: Multimodal treatment strategy including perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) has been accepted as the standard of care in gastric cancer (GC). The ideal sequence and type of therapy remain undetermined. METHOD: The National Cancer Database was examined from 2006 to 2016 to identify patients with resectable non-cardia gastric cancer. Patient outcomes were compared based on the receipt of PEC, POCR, and POC. This comparison was repeated in a sub-group of patients who received optimal treatment. Optimal treatment was defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection and standard radiation dose (45 Gy). Kaplan-Meier test, log-rank test, and multivariable analysis (MVA) were performed. RESULTS: We identified 9589 patients. Median survival was greater in the PEC group followed by POCR and POC (60.6, 42.3, and 31.2 months, respectively). On MVA, factors associated with worse overall survival included age above median (≥ 63 years), Charlson-Deyo score of ≥ 1, non-academic/research program, poorly differentiated/undifferentiated grade, positive margins, and positive lymph nodes. Both PEC and POCR were associated with improved survival when compared to POC (HR 0.78 and 0.79; p < 0.001). When compared with PEC, no significant difference was noted with POCR (HR 1.01; p = 0.987). These results were maintained in optimally treated cohort (n = 3418). CONCLUSION: In patients with resectable non-cardia gastric cancer, both perioperative chemotherapy and postoperative chemoradiation therapy were associated with improved survival when compared to postoperative chemotherapy. No difference was noted between perioperative chemotherapy and postoperative chemoradiation therapy. These results were maintained in the optimally treated cohort.

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

OBJECTIVE: Early 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 EGCA using single-cell RNA sequencing (scRNA-seq). DESIGN: scRNA-seq was conducted on 95 551 cells from endoscopic biopsies of low-grade intraepithelial neoplasia, well/moderately/poorly differentiated EGCA and their paired adjacent nonmalignant biopsy samples. Large-scale clinical samples and functional experiments were employed. RESULTS: Integrative analysis of epithelial cells revealed that chief cells, parietal cells and enteroendocrine cells were rarely detected in the malignant epithelial subpopulation, whereas gland and pit mucous cells and AQP5+ stem cells were predominant during malignant progression. Pseudotime and functional enrichment analyses showed that the WNT and NF-κB signalling pathways were activated during the transition. Cluster analysis of heterogeneous malignant cells revealed that NNMT-mediated nicotinamide metabolism was enriched in gastric mucin phenotype cell population, which was associated with tumour initiation and inflammation-induced angiogenesis. Furthermore, the expression level of NNMT was gradually increased during the malignant progression and associated with poor prognosis in cardia adenocarcinoma. Mechanistically, NNMT catalysed the conversion of nicotinamide to 1-methyl nicotinamide via depleting S-adenosyl methionine, which led to a reduction in H3K27 trimethylation (H3K27me3) and then activated the WNT signalling pathway to maintain the stemness of AQP5+ stem cells during EGCA malignant progression. CONCLUSION: Our study extends the understanding of the heterogeneity of EGCA and identifies a functional NNMT+/AQP5+ population that may drive malignant progression in EGCA and could be used for early diagnosis and therapy.

Cardia and non-cardia gastric cancer risk associated with Helicobacter pylori in East Asia and the West: A systematic review, meta-analysis, and estimation of population attributable fraction.

OBJECTIVES: To assess the region-specific relative risk of cardia/non-cardia gastric cancer (CGC/NCGC) associated with Helicobacter pylori (H. pylori) and quantify its contribution to gastric cancer burden using population attributable fraction (PAF). METHODS: PubMed, EMBASE, Web of Science, and Cochrane Central databases were searched by two reviewers until April 20, 2022. The association between H. pylori infection and NCGC/CGC was assessed using pooled odds ratios (ORs) with 95% confidence intervals (CIs). PAF was calculated using the formula of H. pylori prevalence and the pooled OR. RESULTS: One hundred and eight studies were included. A significant association was observed between H. pylori infection and NCGC in East Asia (OR, 4.36; 95% CI: 3.54-5.37) and the West (OR, 4.03; 95% CI: 2.59-6.27). Regarding CGC, a significant association was found only in East Asia (OR, 2.86; 95% CI: 2.26-3.63), not in the West (OR, 0.80; 95% CI: 0.61-1.05). For studies with a follow-up time of ≥10 years, pooled ORs for NCGC and CGC in East Asia were 5.58 (95% CI: 4.08-7.64) and 3.86 (95% CI: 2.69-5.55), respectively. Pooled OR for NCGC was 6.80 (95% CI: 3.78-12.25) in the West. PAFs showed that H. pylori infection accounted for 71.2% of NCGC, 60.7% of CGC in East Asia, and 73.2% of NCGC in the West. CONCLUSIONS: Gastric cancer burden associated with H. pylori infection exhibits important geographical differences. Prolonged follow-up period could overcome the underestimation of the magnitude of the association between H. pylori infection and CGC/NCGC. Customized strategies for H. pylori screening and eradication should be implemented to prevent gastric cancer.

Does non-metastatic gastric cancer of the cardia warrant a different treatment strategy?

BACKGROUND: Multimodal treatment strategies with surgery as its centerpiece have been accepted as the standard of care in nonmetastatic cardia gastric cancer (CGC). There remains a lack of consensus regarding the optimal multimodal treatment strategy. METHOD: We queried National Cancer Database from 2004 to 2016 to identify patients with resected nonmetastatic CGC who received perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), or postoperative chemotherapy (POC). A subgroup analysis was performed in optimally treated patients defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection, and standard radiation dose (45 Gy). Kaplan-Meier, Univariate analysis (UVA), and Multivariable analysis (MVA) were performed. RESULTS: We identified 2387 patients. Median survival was 38.8 months in the PEC group, 36 months in the POCR group, and 32.3 months in the POC group (p = 0.1025). On UVA, patients treated with PEC had an association with improved survival (HR, 0.83; p = 0.037) when compared with POC. On MVA, no significant difference was noted in overall survival (OS) between PEC, POCR, and POC, similar to subgroup analysis of optimally treated cohort. CONCLUSION: OS rate in nonmetastatic CGC is not significantly different between patients receiving PEC, POCR, or POC.

Multivariate longitudinal data for survival analysis of cardiovascular event prediction in young adults: insights from a comparative explainable study.

BACKGROUND: Multivariate longitudinal data are under-utilized for survival analysis compared to cross-sectional data (CS - data collected once across cohort). Particularly in cardiovascular risk prediction, despite available methods of longitudinal data analysis, the value of longitudinal information has not been established in terms of improved predictive accuracy and clinical applicability. METHODS: We investigated the value of longitudinal data over and above the use of cross-sectional data via 6 distinct modeling strategies from statistics, machine learning, and deep learning that incorporate repeated measures for survival analysis of the time-to-cardiovascular event in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We then examined and compared the use of model-specific interpretability methods (Random Survival Forest Variable Importance) and model-agnostic methods (SHapley Additive exPlanation (SHAP) and Temporal Importance Model Explanation (TIME)) in cardiovascular risk prediction using the top-performing models. RESULTS: In a cohort of 3539 participants, longitudinal information from 35 variables that were repeatedly collected in 6 exam visits over 15 years improved subsequent long-term (17 years after) risk prediction by up to 8.3% in C-index compared to using baseline data (0.78 vs. 0.72), and up to approximately 4% compared to using the last observed CS data (0.75). Time-varying AUC was also higher in models using longitudinal data (0.86-0.87 at 5 years, 0.79-0.81 at 10 years) than using baseline or last observed CS data (0.80-0.86 at 5 years, 0.73-0.77 at 10 years). Comparative model interpretability analysis revealed the impact of longitudinal variables on model prediction on both the individual and global scales among different modeling strategies, as well as identifying the best time windows and best timing within that window for event prediction. The best strategy to incorporate longitudinal data for accuracy was time series massive feature extraction, and the easiest interpretable strategy was trajectory clustering. CONCLUSION: Our analysis demonstrates the added value of longitudinal data in predictive accuracy and epidemiological utility in cardiovascular risk survival analysis in young adults via a unified, scalable framework that compares model performance and explainability. The framework can be extended to a larger number of variables and other longitudinal modeling methods. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00005130, Registration Date: 26/05/2000.

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.

Gastric Cancer Risk in Patients with Long-Term Use of Proton Pump Inhibitors: A Systematic Review and Meta-Analysis of Observational and Interventional Studies.

BACKGROUND: A growing number of studies that differ in design, quality, and results report an association between the use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC). We conducted a systematic review and meta-analysis, when possible, of observational and interventional studies examining PPI use and risk of GC. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified studies fully published in English through January 2023 using MeSH and non-MeSH keywords. We used random effects models to calculate pooled risk estimates with 95% confidence interval (CI) between PPI use and overall GC, cardia GC, and non-cardia GC. We estimated heterogeneity (I2) among studies. We examined the effect of study design and quality, GC site, H. pylori infection, and PPI duration. We assessed quality using the Newcastle-Ottawa Quality Assessment Scale and Risk Of Bias In Non-randomized Studies of Interventions. RESULTS: We identified 15 observational studies, of which 13 were included in the meta-analysis (six cohort and seven case-control). There was a modest 1.67-fold increase in overall GC risk (95% CI 1.39, 2.00) and no increase in cardia GC risk [odds ratio (OR) 1.12; 95% CI 0.80, 1.56] with PPI use. However, there was high heterogeneity (I2 = 61.3%, p = 0.004) among studies. All but one study had at least moderate risk of bias. In the six studies accounting for H. pylori, GC risk associated with PPI use increased slightly (OR 1.78; 95% CI 1.25, 2.52). Duration response was not reported consistently to allow pooled estimates. We identified only one interventional randomized controlled study that included GC as an outcome of interest, and it did not show increased GC risk. CONCLUSIONS: The overall available evidence is not supportive of a meaningful change in GC risk, either cardia or non-cardia, with PPI use.

A study on the congruence and proximity of the sling and clasp fibres at the cardio-esophageal junction of the stomach.

BACKGROUND AND AIM: The cardio-oesophageal sphincter that is located in close longitudinal proximity to the origin of the lesser curvature of the stomach has a unique pattern of external muscle fibres whose inner oblique layer would normally form an elongated sling and the middle partially circular layer would form a projecting clasp into the already existing muscular sling of the former congruently, which would result in the formation of an anatomical sphincter in that area that would normally be devoid of the external longitudinal muscle layer coat. Certain authors have disagreed with the notion of this standard literature and have proposed that the clasp and sling fibres need not necessarily be congruent and may even remain independent of each other with partial contributions from the longitudinal muscle layers as well that may arise tangentially in different populations, which may in turn contribute to reflux oesophagitis in that population. Hence, the clasp and sling fibre muscular patterns were observed in six formalin-embalmed cadavers at the department of anatomy in a tertiary care institute as part of routine dissections in series, and the findings were then reported. FINDINGS: At the junction of the lesser curvature of the stomach with the oesophagus, all six cadavers showed a longitudinal sling pattern as opposed to the conventional oblique sling. The circular muscle layer was found to be merged with the outer longitudinal muscle layer to form the sling that pulled away from the clasp, resulting in a loss of congruency for the same. The clasp fibres, however, were found to be contributed by the inner oblique muscle layer. The conventional perpendicular or tangential merging of the clasp with the sling was not observed; instead, an obtuse, blunt angular merging of the clasp with the sling was observed. DISCUSSION: The deviation of the sling from the clasp could indicate a lack of a proper fit between them at the cardio-oesophageal sphincter. The lack of robustness in the attachment of the clasp to the sling may possibly contribute to the diminished taut pull of the clasp in this subset of the population. These would be significant determinants for a predisposition to reflux oesophagitis and Barrett's oesophagus.

Evaluation and Management of Achalasia Cardia in Children: A Retrospective Observational Study.

Background: Achalasia cardia is a neuromuscular disorder of unknown etiology characterized by aperistalsis of the body of the esophagus and failure of relaxation of the lower esophageal sphincter. The diagnosis of achalasia cardia is delayed due to the rarity and the ability to mimic other common conditions in children. Hence, a study was conducted to evaluate the clinical presentation and the management of achalasia cardia in children. Materials and Methods: A retrospective observational study was conducted in the department of pediatric surgery at a tertiary center. The children with achalasia cardia who presented between January 2014 and December 2021 were included. Results: A total of 12 patients were treated for achalasia cardia during the study period. All children presented with recurrent episodes of vomiting, whereas dysphagia was seen in six (50%) children. Eighty-three percent of the children presented with a history of weight loss, whereas failure to thrive was seen in nine (75%) children. Five (42%) children were managed as gastroesophageal reflux disease (GERD) for more than a year before presenting to us. Three (25%) children underwent open cardiomyotomy with Thal fundoplication and the rest nine (75%) underwent laparoscopic cardiomyotomy. All are thriving well. Conclusion: Achalasia is an important differential diagnosis in children with suspected GERD. The most common symptom of achalasia cardia is vomiting followed by dysphagia. Weight loss and failure to thrive are important presenting features in children with achalasia which are uncommon in adults. Cardiomyotomy without fundoplication is safe and effective to treat achalasia cardia in children without having any extra complications.

The outcome of 100 patients with achalasia cardia following laparoscopic Heller myotomy with blunt dissection technique.

Background: Laparoscopic Heller myotomy (LHM) can be performed by blunt dissection technique (BDT). Only a few studies have assessed long-term outcomes and relief of dysphagia following LHM. The study reviews our long-term experience following LHM by BDT. Methods: This retrospective study was analysed from a prospectively maintained database (from 2013 to 2021) of a single unit of the Department of Gastrointestinal Surgery at G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi. The myotomy was performed by BDT in all patients. A fundoplication was added in selected patients. Post-operative Eckardt score >3 was considered treatment failure. Results: A total of 100 patients underwent surgery during the study period. Of them, 66 patients underwent LHM, 27 underwent LHM with Dor fundoplication and 7 underwent LHM with Toupet fundoplication. The median length of myotomy was 7 cm. The mean operative time was 77 ± 29.27 min and the mean blood loss of 28.05 ± 16.06 ml. Five patients had intraoperative oesophageal perforation. The median length of hospital stay was 2 days. There was no hospital mortality. The post-operative integrated relaxation pressure (IRP) was significantly lower than the mean pre-operative IRP (9.78 vs. 24.77). Eleven patients developed treatment failure, of which ten patients presented with recurrence of dysphagia. There was no difference in symptom-free survival amongst various types of achalasia cardia (P = 0.816). Conclusion: LHM performed by BDT has a 90% success rate. Complication using this technique is rare, and recurrence post-surgery can be managed with endoscopic dilatation.

Use real-time near-infrared fluorescence during Heller's cardiomyotomy for achalasia cardia.

Laparoscopic Heller's cardiomyotomy is the surgical procedure of choice in the management of oesophageal achalasia. It is critical to confirm the completeness of the myotomy and mucosal integrity at the conclusion of the procedure. This is conventionally achieved by intraoperative endoscopy and dynamic air leak test. Other modalities that can be used to confirm the myotomy and the integrity of the mucosa at the myotomy site are oesophageal manometry and a methylene blue dye study, respectively. Indocyanine green (ICG) has been in clinical use for more than six decades. The real-time integration of ICG fluorescence with laparoscopy is a relatively new breakthrough. Here, we present a novel method of using real-time near-infrared ICG fluorescence for confirming the completeness of the myotomy and mucosal integrity at the myotomy site post laparoscopic Heller's myotomy. This is the first report on the use of ICG in laparoscopic Heller's cardiomyotomy that we are aware of.

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.

Associations of white matter hyperintensities with networks of gray matter blood flow and volume in midlife adults: A coronary artery risk development in young adults magnetic resonance imaging substudy.

White matter hyperintensities (WMHs) are emblematic of cerebral small vessel disease, yet effects on the brain have not been well characterized at midlife. Here, we investigated whether WMH volume is associated with brain network alterations in midlife adults. Two hundred and fifty-four participants from the Coronary Artery Risk Development in Young Adults study were selected and stratified by WMH burden into Lo-WMH (mean age = 50 ± 3.5 years) and Hi-WMH (mean age = 51 ± 3.7 years) groups of equal size. We constructed group-level covariance networks based on cerebral blood flow (CBF) and gray matter volume (GMV) maps across 74 gray matter regions. Through consensus clustering, we found that both CBF and GMV covariance networks partitioned into modules that were largely consistent between groups. Next, CBF and GMV covariance network topologies were compared between Lo- and Hi-WMH groups at global (clustering coefficient, characteristic path length, global efficiency) and regional (degree, betweenness centrality, local efficiency) levels. At the global level, there were no between-group differences in either CBF or GMV covariance networks. In contrast, we found between-group differences in the regional degree, betweenness centrality, and local efficiency of several brain regions in both CBF and GMV covariance networks. Overall, CBF and GMV covariance analyses provide evidence that WMH-related network alterations are present at midlife.

Cholangiocarcinoma presenting as dysphagia and misdiagnosed as gastritis: a case report.

BACKGROUND: Heterotopic tumor is a rare disease. Thus far, no cases of heterotopic cholangiocarcinoma have been reported in the world. Cholangiocarcinoma mainly metastasizes by direct invasion, and it can lead to liver metastasis in its advanced stage. There were few clinical cases of gastric metastasis in advanced tumors, mainly seen in breast cancer, lung cancer, liver cancer, malignant melanoma, choriocarcinoma, and hematological tumors. Metastases of cholangiocarcinoma to the stomach also are exceptionally rare. CASE PRESENTATION: A 58-year-old man was admitted to the hospital because of difficulty swallowing for one year. Upon gastroscopy, we found the tumor at the region of the cardia and gastric fundus. Macroscopical appearance of the tumor suggested its malignant nature. Computed tomography (CT) findings showed that the wall of the cardia, fundus, and stomach body were thickened, suggesting a tumor. Because the patient had obvious difficulty swallowing, we invited cardiothoracic surgeons for consultation. They considered that the patient had definite mechanical obstruction in the lower esophagus; hence, they performed an operation. Immunohistochemical staining revealed low-to-medium differentiated adenocarcinoma (containing mucinous adenocarcinoma components) of biliary origin. CONCLUSIONS: We highlight the importance of the endoscopic biopsy of gastric tumor. However, when its results are inconsistent with the clinician's judgment, further examination is required. Endoscopic ultrasonography and enhanced CT may be a good choice. If necessary, on the premise of patient acceptance, the diagnosis could be confirmed after surgical excision. Here we report a case of a patient with heterotopic cholangiocarcinoma in the gastric fundus. The most common tissue ectopias in the digestive tract include esophagogastric gastric mucosal ectopia, duodenal gastric mucosal ectopia, and gastric mucosal small intestinal ectopia. Thus far, there have been no reports of ectopic cholangiocarcinoma and associated cancer in the stomach. In addition, metastases of cholangiocarcinoma to the stomach are also exceptionally rare, and most of them are due to a direct invasion. The discovery of the primary lesion is an important clue for the reliable diagnosis in such cases.

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.