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Stomach Cancer

Gastric cancer (cancer of the stomach) is a disease in which malignant cells arise in the tissues of the stomach. Early symptoms can include indigestion, feeling bloated after eating, mild nausea, loss of appetite, or heartburn. In more advanced stages symptoms may include blood in the stool, vomiting, weight loss, or pain in the stomach. Known risk factors include prior stomach infection by Helicobacter pylori, smoking, frequent diet of dry salted foods, Menetrier's disease, and familial polyposis. Most cancers of the stomach are adenocarcinomas of which there are many sub-types.

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Information for Patients and the Public
Information for Health Professionals / Researchers
Helicobacter pylori and cancer
Gastrointestinal System Cancers
Latest Research Publications

Information for Patients and the Public (16 links)


Information for Health Professionals / Researchers (16 links)

See also: CDH1 Genetic Information

Helicobacter pylori and cancer (4 links)

    UK Helicobacter Pylori

    Patient UK
    Quality indicator: based on clear editorial policy, regular updates etc.PatientUK content is peer reviewed. Content is reviewed by a team led by a Clinical Editor to reflect new or updated guidance and publications. Further info.
    A referenced article about Helicobacter Pylori for health professionals.

    UK Helicobacter pylori - patients' information

    British Society of Gastroenterology
    Article about Helicobacter pylori, including some simple diagrams.

    USA Helicobacter pylori and Cancer

    National Cancer Institute
    A referenced fact sheet giving an overview of the Helicobacter pylori bacterium and answering a number of questions about its link to gastric cancer.

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Yanagita T, Kusanagi H
Safety and Effectiveness of Enoxaparin as Venous Thromboembolism Prophylaxis after Gastric Cancer Surgery in Japanese Patients.
Am Surg. 2016; 82(12):1232-1237 [PubMed] Related Publications
Routine prophylaxis for venous thromboembolism (VTE) has been recommended after surgery not only in the West but also in Asia recently. The primary objective of this study was to investigate the safety and effectiveness of enoxaparin as a prophylaxis in patients undergoing distal, proximal, or total gastrectomy (TG) for gastric cancers. A total of 565 patients who underwent gastrectomy for gastric cancer were reviewed retrospectively. About 256 patients received postoperative prophylaxis with enoxaparin (2000 international unit twice daily for at least six days) and compression stockings; these patients were assigned to the enoxaparin group. About 257 patients comprised a historical control group, who used only compression stockings as a thromboprophylaxis. All patients underwent the same rehabilitation programs during the perioperative period. None of the patients developed symptomatic venous thromboembolism in either the enoxaparin group or the control group. The complication rate of bleeding was not significantly different between the two groups. Only one patient who used three antiplatelet agents concomitantly with enoxaparin required reoperation for anastomotic site bleeding. The usage of enoxaparin for venous thromboembolism prophylaxis is safe for Japanese patients after gastrectomy. But, cautious application is still needed especially when used concomitantly with other antiplatelet agents.

Jiang B, Li S, Jiang Z, Shao P
Gastric Cancer Associated Genes Identified by an Integrative Analysis of Gene Expression Data.
Biomed Res Int. 2017; 2017:7259097 [PubMed] Free Access to Full Article Related Publications
Gastric cancer is one of the most severe complex diseases with high morbidity and mortality in the world. The molecular mechanisms and risk factors for this disease are still not clear since the cancer heterogeneity caused by different genetic and environmental factors. With more and more expression data accumulated nowadays, we can perform integrative analysis for these data to understand the complexity of gastric cancer and to identify consensus players for the heterogeneous cancer. In the present work, we screened the published gene expression data and analyzed them with integrative tool, combined with pathway and gene ontology enrichment investigation. We identified several consensus differentially expressed genes and these genes were further confirmed with literature mining; at last, two genes, that is, immunoglobulin J chain and C-X-C motif chemokine ligand 17, were screened as novel gastric cancer associated genes. Experimental validation is proposed to further confirm this finding.

Khan S, Mikhail S, Xiu J, Salem ME
Molecular biology of gastroesophageal cancers: opportunities and challenges.
Clin Adv Hematol Oncol. 2017; 15(1):75-82 [PubMed] Related Publications
Gastroesophageal (GE) malignancies make up a significant and growing segment of newly diagnosed cancers. Approximately 80% of patients who have GE cancers die within 5 years of diagnosis, which means that effective treatments for these malignancies need to be found. Currently, targeted therapies have a minimal role in this disease group. Intensive study of the molecular biology of GE cancers is a relatively new and ongoing venture, but it has already led to a significant increase in our understanding of these malignancies. This understanding, although still limited, has the potential to enhance our ability to develop targeted therapies in conjunction with the ability to identify actionable gene mutations and perform genomic profiling to predict drug resistance. Several cell surface growth factor receptors have been found to play a prominent role in GE cancer cell signaling. This discovery has led to the approval of 2 agents within the last few years: trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody used in the first-line treatment of HER2-positive GE cancers, and ramucirumab, an anti-vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody that is currently used in later lines of therapy. This review discusses the current state of molecular testing in GE cancers, along with the known molecular biology and current and investigational treatments. The development of trastuzumab and ramucirumab represents a significant advance in our ability to make use of GE tumor molecular profiles. As our understanding of the impact of molecular aberrations on drug effectiveness and disease outcomes increases, we anticipate improved therapy for patients with GE cancers.
Related: Cancer of the Esophagus Esophageal Cancer Signal Transduction

Kinsinger LA, Garber JC, Whipple O
A Review of Sleeve Gastrectomy Specimen Histopathology.
Am Surg. 2016; 82(11):1101-1104 [PubMed] Related Publications
With the increasing popularity of sleeve gastrectomy, many stomach specimens are being evaluated. Understanding the significance and treatment for unexpected pathology is important. This study examines the incidence of relevant histopathology of sleeve gastrectomy specimens. It evaluates previous data for each histopathology and provides recommendations for treatment. In this study, a retrospective review was performed for 241 patients who underwent sleeve gastrectomy from 2009 to 2014 at a single institution. Of the specimens, 122 had no significant histopathology, 91 had gastritis, 13 had lymphoid aggregates, 5 had hyperplasia, 3 had intestinal metaplasia, 3 had gastrointestinal stromal tumors (GISTs), and 3 had gastric polyps. Of the GISTs all had a low mitotic rate and the size of the tumor ranged from 1.5 to 4.5 cm. The findings of metaplasia may be a marker for increased risk of malignancy and may require additional surveillance. The findings of GIST may warrant interval imaging to survey for recurrence, though the likelihood of recurrence for the tumors in this study is less than 2 per cent based on previous studies.
Related: Gastrointestinal Stromal Tumors

Dai L, Wang G, Pan W
Andrographolide Inhibits Proliferation and Metastasis of SGC7901 Gastric Cancer Cells.
Biomed Res Int. 2017; 2017:6242103 [PubMed] Free Access to Full Article Related Publications
To explore the mechanisms by which andrographolide inhibits gastric cancer cell proliferation and metastasis, we employed the gastric cell line SGC7901 to investigate the anticancer effects of andrographolide. The cell survival ratio, cell migration and invasion, cell cycle, apoptosis, and matrix metalloproteinase activity were assessed. Moreover, western blotting and real-time PCR were used to examine the protein expression levels and the mRNA expression levels, respectively. The survival ratio of cells decreased with an increasing concentration of andrographolide in a dose-dependent manner. Consistent results were also obtained using an apoptosis assay, as detected by flow cytometry. The cell cycle was blocked at the G2/M2 phase by andrographolide treatment, and the proportion of cells arrested at G1/M was enhanced as the dose increased. Similarly, wound healing and Transwell assays showed reduced migration and invasion of the gastric cancer cells at various concentrations of andrographolide. Andrographolide can inhibit cell proliferation, invasion, and migration, block the cell cycle, and promote apoptosis in SGC7901 cells. The mechanisms may include upregulated expression of Timp-1/2, cyclin B1, p-Cdc2, Bax, and Bik and downregulated expression of MMP-2/9 and antiapoptosis protein Bcl-2.

Negovan A, Iancu M, Moldovan V, et al.
The Interaction between GSTT1, GSTM1, and GSTP1 Ile105Val Gene Polymorphisms and Environmental Risk Factors in Premalignant Gastric Lesions Risk.
Biomed Res Int. 2017; 2017:7365080 [PubMed] Free Access to Full Article Related Publications
The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions (p = 0.01) as well as in premalignant lesions (p = 0.01). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-negative patients (OR = 2.27, 95% CI: 1.20-4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19-3.83). The GSTT1 deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72-4.74). The combined GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00-2.97). The wild-type GSTP1 Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37-0.98). In conclusion, the GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions.
Related: GSTP1 GSTT1 GSTM1

Prouet P, Giri S, Wiedower E, et al.
Addition of Rituximab to Chemotherapy Reduced the Rate of Surgery for Gastric-DLBCL Without Increasing Early Mortality.
Anticancer Res. 2017; 37(2):813-817 [PubMed] Related Publications
BACKGROUND: We evaluated surgical trends for gastric diffuse large B-cell lymphoma (gDLBCL) before and after the approval of rituximab and whether an association of early mortality existed in patients treated after approval of rituximab.
PATIENTS AND METHODS: We utilized the Surveillance Epidemiology and End Results (SEER) 18 database to extract data on patients with gDLBCL diagnosed between 1983-2012. Primary site-specific cancer-directed surgery using SEER site-specific surgical codes and annual trends were analyzed. Patients were analyzed before and after 2006, the year rituximab gained U.S. Food and Drug Administration approval.
RESULTS: Joinpoint trend analysis showed the sharpest decline in surgical rates between 2000-2010. Adjusted surgical rates computed using poisson regression declined from 54.4% in 1983 to 6.9% in 2012, with an annual percentage change of -8.9% (95% confidence interval=-9.7% to -8.3%; p-value <0.01). No significant mortality increase at 30 and 60 days was found.
CONCLUSION: While rituximab appears to have significantly changed how surgery is utilized for patients with gDLBCL, early mortality was unchanged.
Related: Rituximab (Mabthera) USA

Backman S, Norlén O, Eriksson B, et al.
Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing.
Anticancer Res. 2017; 37(2):705-712 [PubMed] Related Publications
Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.
PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.
RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.
CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.
Related: Everolimus (Afinitor) Cancer of the Pancreas Pancreatic Cancer Signal Transduction MEN1 MTOR

Satoh T, Kaira K, Takahashi K, et al.
Prognostic Significance of the Expression of CD98 (4F2hc) in Gastric Cancer.
Anticancer Res. 2017; 37(2):631-636 [PubMed] Related Publications
BACKGROUND: CD98 expression is high in various human neoplasms. However, the relationship of CD98 expression with the clinicopathological factors of gastric cancer (GC) remains unclear. This study examined CD98 expression and its clinicopathological impact on GC.
PATIENTS AND METHODS: Three hundred and thirty-one patients with surgically resected GC were evaluated. Tumor sections were stained and analyzed using immunohistochemistry to assess CD98 expression.
RESULTS: CD98 was positively expressed in 19% (66/331) of our patient cohort. Increased CD98 expression was significantly associated with advanced GC stage, lymph node metastasis, non-signet histology, lymphatic permeation, and vascular invasion. Positive CD98 expression was also a significant prediction marker for unfavorable prognosis postoperatively. However, CD98 was not identified as GC's independent prognostic predictor.
CONCLUSION: CD98 could be a novel prediction marker for worse prognosis in GC-affected patients. Our data suggests that increased CD98 expression plays an essential role in tumor aggressiveness and metastasis.

Bauer G
Central Signaling Elements of Intercellular Reactive Oxygen/Nitrogen Species-dependent Induction of Apoptosis in Malignant Cells.
Anticancer Res. 2017; 37(2):499-513 [PubMed] Related Publications
Intercellular reactive oxygen/reactive nitrogen species-(ROS/RNS)-dependent induction of apoptosis in malignant cells is discussed as a potential control step during oncogenesis. In previous studies, the mechanism of intercellular apoptosis-inducing signaling was mainly established through the use of specific inhibitors and scavengers. Here, a detailed analysis was carried out based on small interfering ribonucleic acid (siRNA)-mediated knockdown of central players of intercellular ROS/RNS signaling and of the mitochondrial and the FAS receptor-dependent pathway of apoptosis. The data show that transforming growth factor β1, transforming growth factor β receptor, NADPH oxidase-1 (NOX1), NOX1 organizer, and NOX1 activator control the HOCl and the NO/peroxynitrite signaling pathways. Dual oxidase-1 (DUOX1) is specifically involved in HOCl signaling, and NO synthase in NO/peroxynitrite signaling. Both pathways utilize intracellular signal transduction through protein kinase C zeta, sphingomyelinase and central elements of the mitochondrial pathway of apoptosis, whereas the FAS receptor and FAS ligand do not seem to play a role.
Related: Apoptosis Signal Transduction TGFB1

Li WH, Song YC, Zhang H, et al.
Decreased Expression of Hsa_circ_00001649 in Gastric Cancer and Its Clinical Significance.
Dis Markers. 2017; 2017:4587698 [PubMed] Free Access to Full Article Related Publications
Background. It has been reported that circRNAs are differentially expressed in a wide range of cancers and could be used as a new biomarker for diagnosis. However, the correlation between circRNAs and gastric cancer (GC) it is still unclear. Materials and Methods. In this study, by using real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs), we detected the expression level of hsa_circ_0001649 in tissue and serum samples from GC patients. Results. We found that hsa_circ_0001649 expression was significantly downregulated in GC tissue compared with their paired paracancerous histological normal tissues (PCHNTs) (P < 0.01). We next analyzed the expression level of hsa_circ_0001649 in serum samples between preoperative and postoperative GC patients. We found that its level in serum was significantly upregulated after surgery (P < 0.01). The area under the receiver operating characteristic (ROC) curve was 0.834. Moreover, the expression level of hsa_circ_0001649 was significantly correlated with pathological differentiation (P = 0.039). Conclusion. Our test suggested that hsa_circ_0001649 was significantly downregulated in GC and may become a novel potential biomarker in the diagnosis of GC.

Liu Z, Feng F, Guo M, et al.
Distal gastrectomy versus total gastrectomy for distal gastric cancer.
Medicine (Baltimore). 2017; 96(5):e6003 [PubMed] Free Access to Full Article Related Publications
Even though more than a century later, after the first case of gastrectomy has been successfully performed, the best surgical treatment for distal gastric cancer still remains controversial. Thus, the present study was designed to compare the survival impact of distal (DG) or total gastrectomy (TG) for distal gastric cancer. A total of 1262 distal gastric cancer patients were enrolled in current study including 1157 patients who underwent DG and 157 patients who underwent TG. The postoperative complications and 5-year overall survival were compared between the 2 groups. TG group presented a longer surgical time, a higher volume of intraoperative bleeding, and a larger number of excised lymph nodes (all P < 0.05) compared with the DG group. The postoperative complications were comparable (all P >0.05). The 5-year overall survival rate of DG group was significantly higher than that of TG group (67.6% vs 44.3%, P < 0.001). However, multivariate analysis showed that type of resection was not an independent prognostic factor for distal gastric cancer (P > 0.05). The factor-stratified multivariate analysis showed that only in the subgroup of Tumor-node-metastasis staging system (TNM) stage III (P = 0.049), TG was the independent prognostic factor for poor survival. In conclusion, DG was as feasible as TG; however, TG did not increase the survival rate. DG brought better long-term survival than TG in patients with TNM stage III tumor. We recommended that DG should be the optimal surgical procedure for distal gastric cancer under the premise of negative resection margin.

Dore MP, Pes GM, Rocchi C, et al.
Are gastric hyperplastic polyps an additional manifestation in celiac disease?: Results from a retrospective study.
Medicine (Baltimore). 2017; 96(5):e5923 [PubMed] Free Access to Full Article Related Publications
Gastric polyps are frequently reported in patients undergoing upper endoscopic procedures. In this retrospective study, the association between hyperplastic polyps and celiac disease in Northern Sardinia was estimated.Age, gender, body mass index, and medications taken in the 2 preceding months, including proton-pump inhibitors (PPIs), H2 receptor blockers (anti-H2), Helicobacter pylori status, endoscopic findings, and histology from charts of patients undergoing esophago-gastro-duodenoscopy were reviewed. Polyps were classified as hyperplastic, fundic gland, inflammatory, and adenomatous.3.7% (423/11379) patients had celiac disease. Prevalence of gastric polyps was 4.2% (3.8% among celiac vs 4.2% nonceliac patients). Inflammatory polyp was the most common histotype (55.8% and 56.2%) followed by fundic gland polyps (31.4% and 43.7%), hyperplastic (8.7% and 0%), and adenomas, in celiac and nonceliac patients, respectively. Fundic gland polyps were more common in PPI users (odds ratio: 4.06) than in nonusers (2.65, P = 0.001) among celiac and nonceliac patients. Age older than 50, female gender, esophago-gastro-duodenoscopy year, and PPI use were associated with the presence of polyps, whereas active H pylori infection was not.Gastric polyps were common in Sardinian patients undergoing esophago-gastro-duodenoscopy. However, the previously reported association between hyperplastic polyps and celiac disease was not confirmed in our study.

Yuan X, Wang S, Liu M, et al.
Histological and Pathological Assessment of miR-204 and SOX4 Levels in Gastric Cancer Patients.
Biomed Res Int. 2017; 2017:6894675 [PubMed] Free Access to Full Article Related Publications
Gastric cancer is one of the most common cancers and the efficient therapeutic methods are limited. Further study of the exact molecular mechanism of gastric cancer to develop novel targeted therapies is necessary and urgent. We herein systematically examined that miR-204 suppressed both proliferation and metastasis of gastric cancer AGS cells. miR-204 directly targeted SOX4. In clinical tissue research, we determined that miR-204 was expressed much lower and SOX4 expressed much higher in gastric cancer tissues compared with normal gastric tissues. Associated analysis with clinicopathological parameters in gastric cancer patients showed miR-204 was associated with no lymph node metastasis and early tumor stages whereas SOX4 was associated with lymph node metastasis and advanced tumor stages. In addition, miR-204 and SOX4 were negatively correlated in tissues from gastric cancer patients. Our findings examined the important role of miR-204 and SOX4 played in gastric cancer, and they could be used as candidate therapeutic targets for gastric cancer therapy.
Related: MicroRNAs

Wang Y
Identifying key stage-specific genes and transcription factors for gastric cancer based on RNA-sequencing data.
Medicine (Baltimore). 2017; 96(4):e5691 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: To identify gastric cancer (GC)-associated genes and transcription factors (TFs) using RNA-sequencing (RNA-seq) data of Asians.
MATERIALS AND METHODS: The RNA-seq data (GSE36968) were downloaded from Gene Expression Omnibus database, including 6 noncancerous gastric tissue samples, 5 stage I GC samples, 5 stage II GC samples, 8 stage III GC samples, and 6 stage IV GC samples. The gene expression values in each sample were calculated using Cuffdiff. Following, stage-specific genes were identified by 1-way analysis of variance and hierarchical clustering analysis. Upstream TFs were identified using Seqpos. Besides, functional enrichment analysis of stage-specific genes was performed by DAVID. In addition, the underlying protein-protein interactions (PPIs) information among stage IV-specific genes were extracted from STRING database and PPI network was constructed using Cytoscape software.
RESULTS: A total of 3576 stage-specific genes were identified, including 813 specifically up-regulated genes in the normal gastric tissues, 2224 stage I and II-specific genes, and 539 stage IV-specific genes. Also, a total of 9 and 11 up-regulated TFs were identified for the stage I and II-specific genes and stage IV-specific genes, respectively. Functional enrichment showed SPARC, MMP17, and COL6A3 were related to extracellular matrix. Notably, 2 regulatory pathways HOXA4-GLI3-RUNX2-FGF2 and HMGA2-PRKCA were obtained from the PPI network for stage IV-specific genes. In the PPI network, TFs HOXA4 and HMGA2 might function via mediating other genes.
CONCLUSION: These stage-specific genes and TFs might act in the pathogenesis of GC in Asians.
Related: HMGA2 Signal Transduction SPARC

Ribeiro J, Oliveira C, Malta M, Sousa H
Epstein-Barr virus gene expression and latency pattern in gastric carcinomas: a systematic review.
Future Oncol. 2017; 13(6):567-579 [PubMed] Related Publications
METHODS: A systematic review of literature was conducted to identify all published reports regarding the expression of Epstein-Barr Virus (EBV) proteins/transcripts and EBV latency patterns in EBV-associated gastric carcinomas (EBVaGC).
RESULTS: The literature search retrieved 247 papers, of which 25 papers matched the inclusion criteria. The analysis reveals that the most frequently expressed EBV latent proteins are EBNA1 (98.1%) and LMP2A (53.8%), while LMP1 and LMP2B are present in only 10% of cases. Lytic proteins, such as BARF0 and BARF1, and other lytic transcripts are present in almost half of cases.
CONCLUSION: EBVaGC seems to display a unique transcription/latency pattern that does not fit the 'standard' EBV latency patterns and therefore should be further studied to better understand EBVaGC carcinogenesis.

Xu W, Beeharry MK, Liu W, et al.
Preoperative Chemotherapy for Gastric Cancer: Personal Interventions and Precision Medicine.
Biomed Res Int. 2016; 2016:3923585 [PubMed] Free Access to Full Article Related Publications
In spite of the declining incidence of gastric cancer (GC) in recent years, the mortality rate is still high. The asymptomatic nature and nonspecific clinical manifestations combined with the lack of efficient screening programs delay the diagnosis of GC. Therefore, the prevalence of advanced gastric cancer (AGC) has prompted the need for aggressive and intensive treatment options. Among the various treatment options for AGC, surgery is still the mainstay. However, the efficacy of surgery alone is not established. Results from multiple randomized controlled trials suggest that preoperative chemotherapy is promising intervention for the treatment and management of AGC. The main objective of neoadjuvant chemotherapy is to downstage or control micrometastasis in resectable tumor before surgery. On the other hand, conversion chemotherapy refers to surgical treatment aiming at R0 resection after chemotherapy for originally nonresectable or marginally resectable tumors. Nevertheless, preoperative chemoradiotherapy is considered beneficial for AGC patients. Over the last few decades, the combination of chemotherapy and targeted therapy prior to surgery demonstrated great results for the treatment of AGC. The rapid developments in genomics and proteomics have heralded the era of precision medicine. The combination of preoperative chemotherapy and precision medicine may enhance survival in AGC patients.

Kim KM, Kim CY, Hong SM, Jang KY
A primary pure pancreatic-type acinar cell carcinoma of the stomach: a case report.
Diagn Pathol. 2017; 12(1):10 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Acinar cell carcinoma represents only 1-2% of exocrine pancreatic neoplasms. On exceptionally rare occasions, primary acinar cell carcinoma can occur in ectopic locations. Herein, we report a case of pure pancreatic-type acinar cell carcinoma arising in the stomach.
CASE PRESENTATION: A 54-year-old male presented with a gastric submucosal mass detected by endoscopic examination. Laparoscopic wedge resection was performed. Macroscopically, the 2.7 cm yellowish mass was located in the submucosa of the stomach. Microscopically, the tumor was well circumscribed and had a homogeneous acinar architecture. The tumor cells were small and had a minimal amount of cytoplasm. The nuclei of the tumor cells were round to oval with finely dispersed chromatin. The tumor cells were strongly positive for α1-antitrypsin, chymotrypsin, and α1-antichymotrypsin immunostaining, consistent with pancreatic exocrine differentiation. There was no clinical or radiologic evidence of primary pancreatic or head and neck tumors. After surgical resection of the tumor, there was no recurrence or metastasis during 33 months follow-up.
CONCLUSION: In this report, we have presented a rare case of primary pure pancreatic-type acinar cell carcinoma arising in the stomach and suggest that it could be helpful if the pathologist were aware that pancreatic-type acinar cell carcinoma could arise in the stomach as a polypoid submucosal tumor in the routine diagnostic field of gastric endoscopy.

Wan J, Chao L, Lee AC, Chen Q
Higher Expression of ERCC1 May Be Associated with Resistance to Adjuvant Platinum-Based Chemotherapy in Gastric Cancer.
Cancer Invest. 2017; 35(2):85-91 [PubMed] Related Publications
Potential predictive biomarker(s) to respond to chemotherapy in gastric cancer are unclear. Excision repair cross-complementing 1 (ERCC1), a DNA repair enzyme, is associated with clinical outcomes in gastric cancer. Here, we investigated the expression of ERCC1 in gastric cancer with platinum-based chemotherapy after surgery, and the association between ERCC1 expression and clinical parameters was analyzed. Our data showed that high levels of ERCC1 expression were positively associated with resistance to platinum-based chemotherapy but not with lymph node metastasis and pathological stage. In addition, patients with resistance to platinum-based chemotherapy probably had lymph node metastasis and pathological stage.
Related: ERCC1

Liang D, Liang S, Jin J, et al.
Gastric cancer burden of last 40 years in North China (Hebei Province): A population-based study.
Medicine (Baltimore). 2017; 96(2):e5887 [PubMed] Free Access to Full Article Related Publications
Gastric cancer (GC) is the second leading cause of cancer death in China. It is well known that Cixian in Hebei Province is one of the highest risk areas of GC in China and worldwide. This study aims to accurate assessment of GC burden and trend in high-risk area (Hebei Province) from 1973 to 2013. The authors analyzed GC data from 21 population-based cancer registries which represented 15.25% of the entire population of Hebei Province. The collected data were stratified by 5-year age groups, gender, and area. Mortality of GC was extracted from national death surveys from 1973 to 1975, 1990 to 1992, 2004 to 2005, and 2011 to 2013. Trend analysis (1988-2013) in a high-risk area (Cixian) used the Joinpoint Model. The age-period-cohort model was used to estimate the effects of age, period, and birth cohort in GC incidence in Cixian from 1988 to 2013. The crude incidence of GC in 2011 to 2013 was 40.37/100,000 (57.53/100,000 in males and 22.55/100,000 in females). The corresponding age-standardized rate by world age-standard population was 32.18/100,000 (48.87/100,000 in males and 17.53/100,000 in females), which was 2.66-fold (2.81-fold in male and 2.34-fold in female) higher than that in the world (12.1/100,000, 17.4/100,000 in males and 7.5/100,000 in females). Males in rural areas had the highest incidence, with an age-standardized rate of 70.51/100,000. Gastric cardia cancer was primary anatomical subsite which accounting for 59.59% in GC, followed by gastric corpus (13.92%), gastric antrum (11.43%), gastric fundus (4.99%), and overlapping lesion of gastric (4.17%). The age-standardized rate of mortality from GC displayed a significant downward trend (P = 0.019) in Hebei Province from the 1990s (31.44/100,000) to the 2010s (24.63/100,000). In Cixian, the incidence of GC rose from 1988 (38.25/100,000) to 2009 (65.11/100,000). Cixian, where population-based screening of upper gastrointestinal cancer was performed, experienced the increasing rate of GC from 2000 (37.59/100,000) to 2009 (65.11/100,000) and then had a sharp decrease from 2009 to 2013 (55.30/100,000), with annual percentage change of -6.69%. Gastric cardia cancer had an increasing trend from 1988 (6.88/100,000) to 2013 (26.56/100,000). Both age and birth cohort effects played important roles in these changes. In conclusion, males in rural areas had the highest risk of GC. GC mortality rate decreased from the 1990s in Hebei Province. Endoscopic screening project for GC is an effective method of controlling the disease.

Meng X, Ni C, Shen Y, et al.
Differentiating malignant from benign gastric mucosal lesions with quantitative analysis in dual energy spectral computed tomography: Initial experience.
Medicine (Baltimore). 2017; 96(2):e5878 [PubMed] Free Access to Full Article Related Publications
To investigate the value of quantitative analysis in dual energy spectral computed tomography (DESCT) for differentiating malignant gastric mucosal lesions from benign gastric mucosal lesions (including gastric inflammation [GI] and normal gastric mucosa [NGM]). This study was approved by the ethics committee, and all patients provided written informed consent. A total of 161 consecutive patients (63 with gastric cancer [GC], 48 with GI, and 50 with NGM) who underwent dual-phase contrast enhanced DESCT scans in the arterial phase (AP) and portal venous phase (PVP) were included in this study. Iodine concentration (IC) in lesions was derived from the iodine-based material-decomposition images and normalized to that in the aorta to obtain normalized IC (nIC). The ratios of IC and nIC between the AP and PVP were calculated. Diagnostic confidence for GC and GI was evaluated with reviewing the features including gastric wall thickness, focal, and eccentric on the conventional polychromatic images. All statistical analyses were performed by using statistical software SPSS 17.0 (SPSS, Chicago, IL). IC and nIC in GC differed significantly from those in GI and NGM, except for nICAP in comparing GC with GI. Mean nIC values of GC (0.18 ± 0.06 in AP and 0.62 ± 0.16 in PVP) were significantly higher than that of NGM (0.12 ± 0.03 in AP and 0.37 ± 0.08 in PVP) (all P < 0.05). There was also significant difference for IC values in GC, GI, and NGM (24.19 ± 8.27, 19.07 ± 5.82, and 13.61 ± 2.52 mg/mL, respectively, in AP and 28.00 ± 7.01, 24.66 ± 6.55, and 16.94 ± 3.06 mg/mL, respectively, in PVP). Based on Receiver Operating Characteristic Curve analysis, nIC and IC in PVP had high sensitivities of 88.89% and 90.48%, respectively, in differentiating GC from NGM, while the sensitivities were 71.43% and 88.89% during AP. Ratios IC and nIC ratios did not provide adequate diagnostic accuracy with their area under curves less than 0.65. With the conventional features, the diagnostic accuracies for GC and GI were 75.0% and 98.0%, respectively. Quantitative analysis of DESCT imaging parameters for gastric mucosa, such as nIC and IC, is useful for differentiating malignant from benign gastric mucosal lesions.

Bartley AN, Washington MK, Ventura CB, et al.
HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology.
Am J Clin Pathol. 2016; 146(6):647-669 [PubMed] Related Publications
CONTEXT: ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA.
OBJECTIVES: To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making.
DESIGN: The College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology convened an expert panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA.
RESULTS: The panel is proposing 11 recommendations with strong agreement from the open-comment participants.
RECOMMENDATIONS: The panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and a HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance.
CONCLUSIONS: This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results.
Related: Cancer of the Esophagus Esophageal Cancer USA

Gao Z, Wang C, Xue Q, et al.
The cut-off value of tumor size and appropriate timing of follow-up for management of minimal EUS-suspected gastric gastrointestinal stromal tumors.
BMC Gastroenterol. 2017; 17(1):8 [PubMed] Free Access to Full Article Related Publications
BACKGROUD: The detectable rate of minimal gastric GISTs has continuously increased. While the surveillance and management of GIST <2 cm have been deemed controversial or lack evidence-based approaches.  The aim of the current study is to propose a cut-off value of tumor size for treatment policy and the appropriate timing for endoscopic ultrasonography (EUS) follow-up in the minimal EUS-suspected gastric GIST patients.
METHODS: A single-institution retrospective study was performed. 69 patients with EUS-suspected gastric GISTs were studied from November 2008 to March 2015. 69 patients with minimal gastric GISTs ≤2 cm diagnosed by EUS were followed for a mean period of 29 months (range, 12 to 70). An at least 20% increase of the maximal diameter of the tumors was set as a significant change.
RESULTS: During follow-up, Of the 69 minimal EUS-suspected GISTs, 16 (23.2%) showed significant changes in size. 11 out of 69 GISTs (15.9%), 6 out of 43 GISTs (14.0%), 7 out of 30 GISTs (23.3%) showed significant changes in size, at 1 year, 2 years, and more than 3 years respectively. The receiver operating characteristic curve analysis showed that the tumor size cut-off was 9.5 mm. Only 4.7 and 3.7% of gastric EUS-suspected GISTs of <9.5 mm in size showed significant changes at 1 year and 2 years, while 9.5% at more than 3 years. 34.6, 31.3 and 55.6% of gastric EUS-suspected GISTs of ≥ 9.5 mm in size showed significant changes at 1 year, 2 years and more than 3 years.
CONCLUSIONS: Minimal EUS-suspected GISTs, larger than 9.5 mm may be associated with significant progression. The patients with a ≥ 9.5 mm GIST should have a EUS 6-12months, while <9.5 mm GIST may have a EUS extended to every 2-3 years.
Related: Gastrointestinal Stromal Tumors

Zhu Y, Jiang Y, Shi L, et al.
7-O-Geranylquercetin induces apoptosis in gastric cancer cells via ROS-MAPK mediated mitochondrial signaling pathway activation.
Biomed Pharmacother. 2017; 87:527-538 [PubMed] Related Publications
7-O-Geranylquercetin (GQ) is a novel O-alkylated derivate of quercetin. In this study, we evaluated its apoptosis induction effects in human gastric cancer cell lines SGC-7901 and MGC-803 and explored the potential molecular mechanisms. The results demonstrated that GQ lowered viability of SGC-7901 and MGC-803 cells in a dose- and time-dependent manner without apparent cytotoxicity to human gastric epithelial cell line GES-1. GQ could induce apoptosis in SGC-7901 and MGC-803cells, and arrest the gastric cancer cells at G2/M phase. Mechanism study showed that GQ triggered generation of reactive oxygen species (ROS), then activated p38 and JNK signaling pathways, subsequently led to mitochondrial impairment by regulating the expression of Bcl-2, Bcl-xl and Bax, and finally promoted the release of cytochrome c and the activation of caspases to induce apoptosis. In addition, Z-VAD-FMK (caspase inhibitor) could reverse GQ-induced apoptosis. SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor) could rescue GQ-induced cell death and attenuate mitochondrial signal pathway activation. Furthermore, NAC (ROS inhibitor) could rescue GQ-induced cell death, reduce ROS generation, decrease the phosphorylation of p38 and JNK, and then attenuate the activation of mitochondrial signal pathway. Taken together, GQ induces caspase-dependent apoptosis in gastric cancer cells through activating ROS-MAPK mediated mitochondrial signal pathway. This study highlights the potential use of GQ as a gastric cancer therapeutic agent.
Related: Apoptosis Mitochondrial Mutations in Cancer Signal Transduction

Zuo ZK, Gong Y, Chen XH, et al.
TGFβ1-Induced LncRNA UCA1 Upregulation Promotes Gastric Cancer Invasion and Migration.
DNA Cell Biol. 2017; 36(2):159-167 [PubMed] Related Publications
According to recent studies, long noncoding RNA urothelial carcinoma associated 1 (UCA1) is involved in the development and progression of many malignant tumors, including gastric cancer (GC). We validated the detailed role of UCA1 in human GC cell lines and GC tissues so as to determine its exact function and the underlying mechanism of GC invasion and migration. In our research, lncRNA-UCA1 was specifically upregulated in GC tissues and cell lines, and augmented GC cell proliferation, and invasive and migratory capabilities. High UCA1 expression in GC was related with poorer prognosis (poorer invasion depth, lymph node metastasis, advanced TNM [T is for the original (primary) tumor, N for nearby (regional) lymph nodes that are involved, and M for distant metastasis] stage, and shorter overall survival). Epithelial mesenchymal transition (EMT), associated with malignancy of cancers, was reported to be responsible for invasion and migration of cancer cells. Transforming growth factor β1 (TGFβ1)-induced EMT was well evaluated. UCA1 silence reduced the protein levels of EMT-related factors, vimentin and snail, while promoted E-cadherin and zonula occludens-1 protein levels in GC cells; the effect of UCA1 could be partly restored by TGFβ1 treatment. Taken together, UCA1 might regulate the tumor proliferation, invasion, and metastasis under TGFβ1 induction. Taken together, UCA1 might present a potential oncogenic factor by promoting GC cell proliferation, invasion, and migration. UCA1 could serve as a novel biomarker for prognosis and a novel therapeutic target of GC treatment.
Related: TGFB1

Qiu G, Li X, Wei C, et al.
The Prognostic Role of SIRT1-Autophagy Axis in Gastric Cancer.
Dis Markers. 2016; 2016:6869415 [PubMed] Free Access to Full Article Related Publications
Aim. Sirtuin 1 (SIRT1) can induce autophagy through deacetylation of Beclin-1 and other autophagy mediators. However, the relationship between SIRT1 and autophagy in GC has not been defined. Therefore, the aim of this study was to confirm the prognostic value of SIRT1 and Beclin-1 and their relationship in GC patients. Methods. Transmission electron microscopy (TEM) was performed to examine the autophagy in GC patients. Immunohistochemistry was used to examine the expression of SIRT1, Beclin-1 in GC, and adjacent nonneoplastic mucosa. Results. In 7 out of 8 GC patients' samples examined by TEM, more autophagic vesicles were observed in GC tissues compared to adjacent nonneoplastic mucosa tissue. A positive correlation between SIRT1 and Beclin-1 expression was observed. Furthermore, Beclin-1 or SIRT1 expression alone or their combined expression were significantly correlated with advanced clinicopathological parameters. High Beclin-1 and SIRT1 expression alone and their combined high expression predicted shorter overall survival and relapse-free survival. Both high Beclin-1 and SIRT1 expressions were independent prognostic factors for poor survival of GC. Conclusions. Based on our results we can conclude that SIRT1 and Beclin-1 expression alone or in combination can be used as prognostic indicator and may represent new therapeutic targets in GC.
Related: SIRT1

Cao Y, Zhang G, Wang P, et al.
Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer.
BMC Gastroenterol. 2017; 17(1):2 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Individualized therapeutic regimen is a recently intensively pursued approach for targeting diseases, in which the search for biomarkers was considered the first and most important. Thus, the goal of this study was to investigate whether the UGT1A1, ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A genes are underlying biomarkers for gastric cancer, which, to our knowledge, has not been performed.
METHODS: Ninety-eight tissue specimens were collected from gastric cancer patients between May 2012 and March 2015. A multiplex branched DNA liquidchip technology was used for measuring the mRNA expressions of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A. Direct sequencing was performed for determination of UGT1A1 polymorphisms. Furthermore, correlations between gene expressions, polymorphisms and clinicopathological characteristics were investigated.
RESULTS: The expressions of TYMS, TUBB3 and STMN1 were significantly associated with the clinicopathological characteristics of age, gender and family history of gastric cancer, but not with differentiation, growth patterns, metastasis and TNM staging in patients with gastric cancer. No clinical characteristics were correlated with the expressions of ERCC1, BRCA1, RRM1 and TOP2A. Additionally, patients carrying G allele at -211 of UGT1A1 were predisposed to developing tubular adenocarcinoma, while individuals carrying 6TAA or G allele respectively at *28 or -3156 of UGT1A1 tended to have a local invasion.
CONCLUSIONS: The UGT1A1 polymorphism may be useful to screen the risk population of gastric cancer, while TYMS, TUBB3 and STMN1 may be potential biomarkers for prognosis and chemotherapy guidance.
Related: ERCC1

Fujishima H, Etoh T, Hiratsuka T, et al.
Serosal and muscular layers incision technique in laparoscopic surgery for gastric gastrointestinal stromal tumors.
Asian J Endosc Surg. 2017; 10(1):92-95 [PubMed] Related Publications
INTRODUCTION: To minimize the resection of stomach tissue, especially for lesions close to the esophagogastric junction or pyloric ring, we developed laparoscopic wedge resection with the serosal and muscular layers incision technique (SAMIT) for gastric gastrointestinal stromal tumors.
MATERIALS AND SURGICAL TECHNIQUE: SAMIT involves resection of the mucosal and submucosal layers and then an incision in serosal and muscular layers around the tumor. SAMIT is simple and does not require special devices. The data of 13 patients who underwent laparoscopic wedge resection with SAMIT for primary gastric gastrointestinal stromal tumors were reviewed. No intraoperative complications were observed, and postoperative stenosis occurred in only one case of a middle stomach lesion. Adequate oncological resection was performed in all cases.
DISCUSSION: Laparoscopic wedge resection with SAMIT is technically and oncologically safe. It is useful for treating gastric gastrointestinal stromal tumors, including those close to the esophagogastric junction or pyloric ring.
Related: Gastrointestinal Stromal Tumors

Neves Filho EH, de Sant'Ana RO, Nunes LV, et al.
Histopathological regression of gastric adenocarcinoma after neoadjuvant therapy: a critical review.
APMIS. 2017; 125(2):79-84 [PubMed] Related Publications
As the perioperative chemotherapy has been widely implemented on the management of gastric cancer patients, heterogeneity of clinical outcomes has been evidenced in parallel to different histopathological regression pattern of gastric cancer cells. Tumor histological response to preoperative therapy has been graded by various systems in order to categorize the amount of regressive changes induced by chemotherapy in relation to residual tumor. In this context, tumor regression grading (TRG) systems might provide important prognostic information as the variety of tumor response may imply on different clinical outcomes with impact in survival rates. Moreover, gastric cancer behavior varies enormously upon individual factors such as histological classification and tumor anatomic site of involvement that have been shown to affect the TRG interpretation. On the other hand, some studies have assessed the role of molecular markers as a predictor of tumor response to neoadjuvant chemotherapy in terms of TRG. Thus, the aim of this review is to evaluate how TRG has been interpreted in gastric cancer, discuss their clinical and prognostic relevance and also address the molecular markers involved in this process.

Gai L, Liu H, Cui JH, et al.
The allele combinations of three loci based on, liver, stomach cancers, hematencephalon, COPD and normal population: A preliminary study.
Gene. 2017; 605:123-130 [PubMed] Related Publications
The purpose of this study was to examine the specific allele combinations of three loci connected with the liver cancers, stomach cancers, hematencephalon and patients with chronic obstructive pulmonary disease (COPD) and to explore the feasibility of the research methods. We explored different mathematical methods for statistical analyses to assess the association between the genotype and phenotype. At the same time we still analyses the statistical results of allele combinations of three loci by difference value method and ratio method. All the DNA blood samples were collected from patients with 50 liver cancers, 75 stomach cancers, 50 hematencephalon, 72 COPD and 200 normal populations. All the samples were from Chinese. Alleles from short tandem repeat (STR) loci were determined using the STR Profiler plus PCR amplification kit (15 STR loci). Previous research was based on combinations of single-locus alleles, and combinations of cross-loci (two loci) alleles. Allele combinations of three loci were obtained by computer counting and stronger genetic signal was obtained. The methods of allele combinations of three loci can help to identify the statistically significant differences of allele combinations between liver cancers, stomach cancers, patients with hematencephalon, COPD and the normal population. The probability of illness followed different rules and had apparent specificity. This method can be extended to other diseases and provide reference for early clinical diagnosis.
Related: Liver Cancer

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