Gastric cancer is the third leading cause of cancer-related deaths and ranks as the fifth most common cancer worldwide. Incidence and mortality differ depending on the geographical region and gastric ...cancer ranks first in East Asian countries. Although genetic factors, gastric environment, and
infection have been associated with the pathogenicity and development of intestinal-type gastric cancer that follows the Correa's cascade, the pathogenicity of diffuse-type gastric cancer remains mostly unknown and undefined. However, genetic abnormalities in the cell adherence factors, such as E-cadherin and cellular activities that cause impaired cell integrity and physiology, have been documented as contributing factors. In recent years,
infection has been also associated with the development of diffuse-type gastric cancer. Therefore, in this report, we discuss the host factors as well as the bacterial factors that have been reported as associated factors contributing to the development of diffuse-type gastric cancer.
Endoscopic submucosal dissection (ESD) is effective in treating early gastric cancer (EGC). It’s role in the comorbid with more advanced disease is unknown. We sought to evaluate this in a large ...Western cohort.
Consecutive patients who underwent ESD for EGC in a single tertiary Western endoscopy centre over 10 years were prospectively analyzed. The primary outcomes were long term overall survival (OS) and disease-free survival (DFS) up to 5 years. Secondary outcomes were efficacy and serious adverse events (SAE).
ESD for 157 EGC in 149 patients were performed in an elderly and comorbid cohort with mean age 73.7 years and age-adjusted Charleson Comorbidity Index 4.2. Over a median follow-up period of 51.6 months, there was no significant difference in 5-year OS (88.9% vs 77.9%, P = 0.290) and DFS (83.2% vs 75.1%, P = 0.593) between absolute indication (AI) EGC and relative indication (RI) EGC. AI EGC cohort achieved higher en bloc (96.3% vs 87.5%, P = 0.069) and R0 resection rate (93.6% vs 62.5%, P <0.001) when compared to RI EGC. There were no significant differences in SAE (7.3% vs 12.5%, P = 0.363). No mortality or surgical resection ensued from ESD complications.
ESD safely confers DFS in poor surgical candidates with RI EGC in a large Western cohort. Patients who are elderly and comorbid or decline surgical resection may benefit from ESD and avoid the risks of surgery and its long-term sequelae.
Gastric cancer (GC) remains a global challenge due to the lack of early detection and precision therapies. Genkwadaphnin (DD1), a natural diterpene isolated from the bud of Flos GenkWa ...(Thymelaeaceae), serves as a Karyopherin β1 (KPNB1) inhibitor. In this study, we investigated the anti-tumor effect of DD1 in both cell culture and animal models. Our findings reveal that KPNB1, a protein involved in nuclear import, was highly expressed in GC tissues and associated with a poor prognosis in patients. We demonstrated that DD1, alongside the established KPNB1 inhibitor importazole (IPZ), inhibited GC cell proliferation and tumor growth by enhancing both genomic and non-genomic activity of Nur77. DD1 and IPZ reduced the interaction between KPNB1 and Nur77, resulting in Nur77 cytoplasmic accumulation and triggering mitochondrial apoptosis. The inhibitors also increased the expression of the Nur77 target apoptotic genes ATF3, RB1CC1 and PMAIP1, inducing apoptosis in GC cell. More importantly, loss of Nur77 effectively rescued the inhibitory effect of DD1 and IPZ on GC cells in both in vitro and in vivo experiments. In this study, we for the first time explored the relationship between KPNB1 and Nur77, and found KPNB1 inhibition could significantly increase the expression of Nur77. Moreover, we investigated the function of KPNB1 in GC for the first time, and the results suggested that KPNB1 could be a potential target for cancer therapy, and DD1 might be a prospective therapeutic candidate.
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•KPNB1 was highly expressed in gastric cancer tissues and associated with a poor patient prognosis.•KPNB1 inhibitor DD1 potently suppresses GC cell survival and tumor growth.•Nur77 acts as a key determinant of the function of KPNB1 in GC.•KPNB1 represents a potential therapeutic target in GC.•DD1 can be a promising therapeutic drug for GC.
Background and Aim
Magnifying endoscopy with narrow‐band imaging (ME‐NBI) has made a huge contribution to clinical practice. However, acquiring skill at ME‐NBI diagnosis of early gastric cancer (EGC) ...requires considerable expertise and experience. Recently, artificial intelligence (AI), using deep learning and a convolutional neural network (CNN), has made remarkable progress in various medical fields. Here, we constructed an AI‐assisted CNN computer‐aided diagnosis (CAD) system, based on ME‐NBI images, to diagnose EGC and evaluated the diagnostic accuracy of the AI‐assisted CNN‐CAD system.
Methods
The AI‐assisted CNN‐CAD system (ResNet50) was trained and validated on a dataset of 5574 ME‐NBI images (3797 EGCs, 1777 non‐cancerous mucosa and lesions). To evaluate the diagnostic accuracy, a separate test dataset of 2300 ME‐NBI images (1430 EGCs, 870 non‐cancerous mucosa and lesions) was assessed using the AI‐assisted CNN‐CAD system.
Results
The AI‐assisted CNN‐CAD system required 60 s to analyze 2300 test images. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the CNN were 98.7%, 98%, 100%, 100%, and 96.8%, respectively. All misdiagnosed images of EGCs were of low‐quality or of superficially depressed and intestinal‐type intramucosal cancers that were difficult to distinguish from gastritis, even by experienced endoscopists.
Conclusions
The AI‐assisted CNN‐CAD system for ME‐NBI diagnosis of EGC could process many stored ME‐NBI images in a short period of time and had a high diagnostic ability. This system may have great potential for future application to real clinical settings, which could facilitate ME‐NBI diagnosis of EGC in practice.
Genome-wide association studies (GWAS) pinpointed gastric cancer (GC)-associated single-nucleotide polymorphisms (SNPs) and other gene variants not only in genes of the human host but also in genes ...of the bacterial pathogen Helicobacter pylori.Functional studies unraveled the underlying mechanisms by which SNPs in H. pylori virulence factors CagA and serine protease HtrA promote GC development.The 171L/S SNP in HtrA originated in Asia 60 000 to 45 000 years ago after the human migration out-of-Africa and spread to all continents except Africa; the EPIYT mutation in CagA arose before the out-of-Africa migration.
Several single-nucleotide polymorphisms (SNPs) in human chromosomes are known to predispose to cancer. However, cancer-associated SNPs in bacterial pathogens were unknown until discovered in the stomach pathogen Helicobacter pylori. Those include an alanine-threonine polymorphism in the EPIYA-B phosphorylation motif of the injected effector protein CagA that affects cancer risk by modifying inflammatory responses and loss of host cell polarity. A serine-to-leucine change in serine protease HtrA is associated with boosted proteolytic cleavage of epithelial junction proteins and introduction of DNA double-strand breaks (DSBs) in host chromosomes, which co-operatively elicit malignant alterations. In addition, H. pylori genome-wide association studies (GWAS) identified several other SNPs potentially associated with increased gastric cancer (GC) risk. Here we discuss the clinical importance, evolutionary origin, and functional advantage of the H. pylori SNPs. These exciting new data highlight cancer-associated SNPs in bacteria, which should be explored in more detail in future studies.
Several single-nucleotide polymorphisms (SNPs) in human chromosomes are known to predispose to cancer. However, cancer-associated SNPs in bacterial pathogens were unknown until discovered in the stomach pathogen Helicobacter pylori. Those include an alanine-threonine polymorphism in the EPIYA-B phosphorylation motif of the injected effector protein CagA that affects cancer risk by modifying inflammatory responses and loss of host cell polarity. A serine-to-leucine change in serine protease HtrA is associated with boosted proteolytic cleavage of epithelial junction proteins and introduction of DNA double-strand breaks (DSBs) in host chromosomes, which co-operatively elicit malignant alterations. In addition, H. pylori genome-wide association studies (GWAS) identified several other SNPs potentially associated with increased gastric cancer (GC) risk. Here we discuss the clinical importance, evolutionary origin, and functional advantage of the H. pylori SNPs. These exciting new data highlight cancer-associated SNPs in bacteria, which should be explored in more detail in future studies.
The immune microenvironment plays a critical regulatory role in the pathogenesis of Helicobacter pylori (H. pylori). Understanding the mechanisms that drive the transition from chronic inflammation ...to cancer may provide new insights for early detection of gastric cancer. Although chronic inflammation is frequent in precancerous gastric conditions, the monitoring function of the inflammatory microenvironment in the progression from H. pylori-induced chronic inflammation to gastric cancer remains unclear. This literature review summarizes significant findings on how H. pylori triggers inflammatory responses and facilitates cancer development through the immune microenvironment. Furthermore, the implications for future research and clinical applications are also addressed. The review is divided into four main sections: inflammatory response and immune evasion mechanisms induced by H. pylori, immune dysregulation associated with gastric cancer, therapeutic implications, and future perspectives on H. pylori-induced gastric carcinogenesis with a focus on the immune microenvironment.
Background
Since “Helicobacter pylori (H. pylori) infection” was set as the indication in the Japanese Society for Helicobacter Research (JSHR) Guidelines 2009, eradication treatment for H. pylori ...gastritis is covered under insurance since 2013 in Japan, and the number of H. pylori eradication has rapidly increased. Under such circumstances, JSHR has made the third revision to the “Guidelines for diagnosis and treatment of H. pylori infection” for the first time in 7 years.
Methods
The Guideline Committee held 10 meetings. Articles published between the establishment of the 2009 Guidelines and March 2016 were reviewed and classified according to the evidence level; the statements were revised on the basis of this review. After inviting public comments, the revised statements were finalized using the Delphi method.
Results
There was no change in the basic policy that H. pylori infectious disease is an indication for eradication. Other diseases presumed to be associated with H. pylori infection were added as indications. Serum pepsinogen level, endoscopic examination, and X‐ray examination were added to the diagnostic methods. The effects of 1‐week triple therapy consisting of potassium‐competitive acid blocker (P‐CAB), amoxicillin, and clarithromycin have improved, and high eradication rates can also be expected with proton pump inhibitors (PPI) or P‐CAB combined with amoxicillin and metronidazole. If the susceptibility test is not performed, the triple PPI or P‐CAB/amoxicillin/metronidazole therapy should be chosen, because the PPI/amoxicillin/metronidazole combination demonstrated a significantly higher eradication rate than PPI/amoxicillin/clarithromycin. In the proposal for gastric cancer prevention, we divided gastric cancer prevention measures by age from adolescent to elderly, who are at an increased gastric cancer risk, and presented measures for gastric cancer prevention primarily based on H. pylori eradication.
Conclusion
We expect the revised guidelines to facilitate appropriate interventions for patients with H. pylori infection and accomplish its eradication and prevention of gastric cancer.
Helicobacter pylori (H. pylori) leads to chronic gastritis and eventually causes gastric cancer. The prevalence of H. pylori infection is gradually decreasing with improvement of living conditions ...and eradication therapy. However, some reports have described cases of H. pylori‐negative gastric cancers (HpNGC), and the prevalence was 0.42–5.4% of all gastric cancers. Diagnostic criteria of HpNGC vary among the different reports; thus, they have not yet been definitively established. We recommend negative findings in two or more methods that include endoscopic or pathological findings or serum pepsinogen test, and negative urease breath test or serum immunoglobulin G test and no eradication history the minimum criteria for diagnosis of HpNGC. The etiology of gastric cancers, excluding H. pylori infection, is known to be associated with several factors including lifestyle, viral infection, autoimmune disorder and germline mutations, but the main causal factor of HpNGC is still unclear. Regarding the characteristics of HpNGC, the undifferentiated type (UD‐type) is more frequent than the differentiated type (D‐type). The UD‐type is mainly signet ring‐cell carcinoma that presents as a discolored lesion in the lower or middle part of the stomach in relatively young patients. The gross type is flat or depressed. The D‐type is mainly gastric adenocarcinoma of the fundic gland type that presents as a submucosal tumor‐like or flat or depressed lesion in the middle and upper part of the stomach in relatively older patients. Early detection of HpNGC enables minimally invasive treatment which preserves the patient's quality of life. Endoscopists should fully understand the characteristics and endoscopic findings of HpNGC.
•This ESMO Clinical Practice Guideline provides key recommendations for managing gastric cancer.•The guideline covers clinical and pathological diagnosis, staging and risk assessment, treatment and ...follow-up.•Treatment and management algorithms for localised and advanced/metastatic disease are provided.•The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe.•Recommendations are based on available scientific evidence and the authors’ collective expert opinion.
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