[Comparison of CT findings between gastric cancer and gastric lymphoma].

PubMed

Fan, Wei-Jun; Lu, Yan-Chun; Liu, Li-Zhi; Shen, Jing-Xian; Xie, Chuan-Miao; Li, Xian; Zhang, Liang

2008-05-01

It is difficult to discriminate progressive gastric cancer and gastric lymphoma by CT imaging, because incrassate gastric wall, lump in gastric cavity, confined gastric cavity, intumescent lymph node, and distant metastasis can be displayed in both of them. This study was to compare the CT findings between gastric cancer and gastric lymphoma to improve diagnosis of gastric tumors, especially for gastric lymphoma. CT images of 27 patients with pathologically proved progressive gastric cancer and 25 patients with pathologically proved gastric lymphoma were reviewed. Tumor location, appearance, scope of involvement, gastric wall thickness, mucous membrane, mucosal fold, serosa membrane, necrosis, enhancement degree and uniformity, involvement of other organs, and abdominal lymph nodes were observed. White line sign was observed in 23 cases (85.2%) of gastric cancer, but not in the 25 cases of gastric lymphoma. The extent of white line sign in gastric cancers was larger in portal vein phase than in arterial phase. Enhancement degree outside the white line was higher in portal vein phase than in arterial phase in 13 cases (48.1%) of gastric cancer. The extent of involved gastric wall was smaller than 50% of the whole gastric wall in all the 27 cases of gastric cancer, while it was larger than 75% in 23 cases (85.2%) of gastric lymphoma. Gastric mucous membrane ulcer was found in all of the 27 cases (100%) of gastric cancer, while it was found in only 1 case (4.0%) of gastric lymphoma. Intumescent lymph nodes in two or more areas were found in 11 cases (40.0%) of gastric lymphoma, but not in gastric cancer. Intumescent lymph nodes in the retroperitoneal space below renal hilum were found in 8 cases (32%) of gastric lymphoma, but not in gastric cancer. There are some different CT features between gastric cancer and gastric lymphoma, such as white line sign, gastric mucous membrane ulcer, extent of involved gastric wall, location of intumescent lymph nodes surrounding the

Does remnant gastric cancer really differ from primary gastric cancer? A systematic review of the literature by the Task Force of Japanese Gastric Cancer Association.

PubMed

Shimada, Hideaki; Fukagawa, Takeo; Haga, Yoshio; Oba, Koji

2016-04-01

Remnant gastric cancer, most frequently defined as cancer detected in the remnant stomach after distal gastrectomy for benign disease and those cases after surgery of gastric cancer at least 5 years after the primary surgery, is often reported as a tumor with poor prognosis. The Task Force of Japanese Gastric Cancer Association for Research Promotion evaluated the clinical impact of remnant gastric cancer by systematically reviewing publications focusing on molecular carcinogenesis, lymph node status, patient survival, and surgical complications. A systematic literature search was performed using PubMed/MEDLINE with the keywords "remnant," "stomach," and "cancer," revealing 1154 relevant reports published up to the end of December 2014. The mean interval between the initial surgery and the diagnosis of remnant gastric cancer ranged from 10 to 30 years. The incidence of lymph node metastases at the splenic hilum for remnant gastric cancer is not significantly higher than that for primary proximal gastric cancer. Lymph node involvement in the jejunal mesentery is a phenomenon peculiar to remnant gastric cancer after Billroth II reconstruction. Prognosis and postoperative morbidity and mortality rates seem to be comparable to those for primary proximal gastric cancer. The crude 5-year mortality for remnant gastric cancer was 1.08 times higher than that for primary proximal gastric cancer, but this difference was not statistically significant. In conclusion, although no prospective cohort study has yet evaluated the clinical significance of remnant gastric cancer, our literature review suggests that remnant gastric cancer does not adversely affect patient prognosis and postoperative course.

Gastric cancer and family history.

PubMed

Choi, Yoon Jin; Kim, Nayoung

2016-11-01

Gastric cancer is associated with high morbidity and mortality rates worldwide. Identifying individuals at high risk is important for surveillance and prevention of gastric cancer. Having first-degree relatives diagnosed with gastric cancer is a strong and consistent risk factor for gastric cancer, but the pathogenic mechanisms behind this familial aggregation are unclear. Against this background, we reviewed the risk factors for gastric cancer in those with a first-degree relative with gastric cancer, and the possible causes for familial clustering of gastric cancer including bacterial factors, inherited genetic susceptibility, environmental factors or a combination thereof. Among individuals with a family history, current or past Helicobacter pylori infection, having two or more first-degree affected relatives or female gender was associated with an increased risk of developing gastric cancer. To date, no specific single nucleotide polymorphism has been shown to be associated with familial clustering of gastric cancer. H. pylori eradication is the most important strategy for preventing gastric cancer in first-degree relatives of gastric cancer patients, particularly those in their 20s and 30s. Early H. pylori eradication could prevent the progression to intestinal metaplasia and reduce the synergistic effect on gastric carcinogenesis in individuals with both H. pylori infection and a family history. Endoscopic surveillance is also expected to benefit individuals with a family history. Further large-scale, prospective studies are warranted to evaluate the cost-effectiveness and optimal time point for endoscopy in this population. Moreover, genome-wide association studies that incorporate environmental and dietary factors on a 'big data' basis will increase our understanding of the pathogenesis of gastric cancer.

Familial Gastric Cancers.

PubMed

Setia, Namrata; Clark, Jeffrey W; Duda, Dan G; Hong, Theodore S; Kwak, Eunice L; Mullen, John T; Lauwers, Gregory Y

2015-12-01

Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%-3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. ©AlphaMed Press.

Downregulation of STARD8 in gastric cancer and its involvement in gastric cancer progression

PubMed Central

Ma, Jinguo; Chen, Jing; Zhi, Yu; Li, Zhenhua; Dai, Dongqiu

2018-01-01

Objective Rho-GTPases play a pivotal role in a wide variety of signal transduction pathways and are associated with a great number of human carcinomas. STARD8, which is a Rho-GTPase-activating protein, has been proposed as a tumor suppressor gene, but its role in gastric cancer remains elusive. In this study, we investigate the expression of STARD8 in gastric cancer and its association with gastric cancer progression. Materials and methods One normal gastric mucosa cell line for example GES1 and six human gastric cancer cell lines such as AGS, MGC803, MKN45, SGC7901, HGC27 and BGC823 were utilized to analyze STARD8 mRNA and protein levels by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. A total of 70 paired gastric tissues including corresponding nonmalignant gastric tissues and cancer tissues were utilized to analyze the protein expression of STARD8 using immunohistochemistry, and the correlation between STARD8 level and clinicopathological features was also evaluated. Results STARD8 was found to be downregulated in primary gastric cancer cells and tissues compared with the normal gastric mucosa cell line, GES1, and corresponding nonmalignant gastric tissues, while its decreased expression was significantly associated with TNM stage, lymph node metastasis and differentiation (p<0.05). Conclusion There is significantly decreased expression of STARD8 in gastric cancer cells and tissues, and its expression may contribute to gastric tumorigenesis. PMID:29849465

Mouse Models of Gastric Cancer

PubMed Central

Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

2013-01-01

Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

Estimation of population-based utility weights for gastric cancer-related health states.

PubMed

Lee, Hyeon-Jeong; Ock, Minsu; Kim, Kyu-Pyo; Jo, Min-Woo

2018-01-01

This study aimed to generate utility weights of gastric cancer-related health states from the perspective of the Korean general population. The Korean adults (age ≥19 years) included in the study were sampled using multistage quota sampling methods stratified by sex, age, and education level. Nine scenarios for hypothetical gastric cancer-related health states were developed and reviewed. After consenting to participate, the subjects were surveyed by trained interviewers using a computer-assisted personal interview method. Participants were asked to perform standard gamble tasks to measure the utility weights of 5 randomly assigned health states (from among nine scenarios). The mean utility weight was calculated for each health state. Three hundred twenty-six of the 407 adults who completed this study were included in the analysis. The mean utility weights from the standard gamble were 0.857 (no gastric cancer with Helicobacter pylori infection), 0.773 (early gastric cancer [EGC] with endoscopic surgery), 0.779 (EGC with subtotal gastrectomy), 0.767 (EGC with total gastrectomy), 0.602 (advanced gastric cancer with subtotal gastrectomy and adjuvant chemotherapy), 0.643 (advanced gastric cancer with total gastrectomy and adjuvant chemotherapy), 0.522 (advanced gastric cancer with extended gastrectomy and adjuvant chemotherapy), 0.404 (metastatic gastric cancer with palliative chemotherapy), and 0.399 (recurrent gastric cancer with palliative chemotherapy). This study was the first to comprehensively estimate the utility weights of gastric cancer-related health states in a general population. The utility weights derived from this study could be useful for future economic evaluations related to gastric cancer interventions.

Association between gastric cancer and the Kyoto classification of gastritis.

PubMed

Shichijo, Satoki; Hirata, Yoshihiro; Niikura, Ryota; Hayakawa, Yoku; Yamada, Atsuo; Koike, Kazuhiko

2017-09-01

Histological gastritis is associated with gastric cancer, but its diagnosis requires biopsy. Many classifications of endoscopic gastritis are available, but not all are useful for risk stratification of gastric cancer. The Kyoto Classification of Gastritis was proposed at the 85th Congress of the Japan Gastroenterological Endoscopy Society. This cross-sectional study evaluated the usefulness of the Kyoto Classification of Gastritis for risk stratification of gastric cancer. From August 2013 to September 2014, esophagogastroduodenoscopy was performed and the gastric findings evaluated according to the Kyoto Classification of Gastritis in a total of 4062 patients. The following five endoscopic findings were selected based on previous reports: atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. A total of 3392 patients (1746 [51%] men and 1646 [49%] women) were analyzed. Among them, 107 gastric cancers were diagnosed. Atrophy was found in 2585 (78%) and intestinal metaplasia in 924 (27%). Enlarged folds, nodularity, and diffuse redness were found in 197 (5.8%), 22 (0.6%), and 573 (17%), respectively. In univariate analyses, the severity of atrophy, intestinal metaplasia, diffuse redness, age, and male sex were associated with gastric cancer. In a multivariate analysis, atrophy and male sex were found to be independent risk factors. Younger age and severe atrophy were determined to be associated with diffuse-type gastric cancer. Endoscopic detection of atrophy was associated with the risk of gastric cancer. Thus, patients with severe atrophy should be examined carefully and may require intensive follow-up. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Predictive model for survival in patients with gastric cancer.

PubMed

Goshayeshi, Ladan; Hoseini, Benyamin; Yousefli, Zahra; Khooie, Alireza; Etminani, Kobra; Esmaeilzadeh, Abbas; Golabpour, Amin

2017-12-01

Gastric cancer is one of the most prevalent cancers in the world. Characterized by poor prognosis, it is a frequent cause of cancer in Iran. The aim of the study was to design a predictive model of survival time for patients suffering from gastric cancer. This was a historical cohort conducted between 2011 and 2016. Study population were 277 patients suffering from gastric cancer. Data were gathered from the Iranian Cancer Registry and the laboratory of Emam Reza Hospital in Mashhad, Iran. Patients or their relatives underwent interviews where it was needed. Missing values were imputed by data mining techniques. Fifteen factors were analyzed. Survival was addressed as a dependent variable. Then, the predictive model was designed by combining both genetic algorithm and logistic regression. Matlab 2014 software was used to combine them. Of the 277 patients, only survival of 80 patients was available whose data were used for designing the predictive model. Mean ?SD of missing values for each patient was 4.43?.41 combined predictive model achieved 72.57% accuracy. Sex, birth year, age at diagnosis time, age at diagnosis time of patients' family, family history of gastric cancer, and family history of other gastrointestinal cancers were six parameters associated with patient survival. The study revealed that imputing missing values by data mining techniques have a good accuracy. And it also revealed six parameters extracted by genetic algorithm effect on the survival of patients with gastric cancer. Our combined predictive model, with a good accuracy, is appropriate to forecast the survival of patients suffering from Gastric cancer. So, we suggest policy makers and specialists to apply it for prediction of patients' survival.

Familial Gastric Cancers

PubMed Central

Setia, Namrata; Clark, Jeffrey W.; Duda, Dan G.; Hong, Theodore S.; Kwak, Eunice L.; Mullen, John T.

2015-01-01

Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%–3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. Implications for Practice: Although the majority of gastric adenocarcinomas are sporadic with many of those related to chronic Helicobacter pylori infection, approximately 10% of the cases show familial aggregation, and a specific hereditary cause is determined in 1%–3% cases. This review describes the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. Ultimately, a better understanding of the biology of these conditions should allow early identification and intervention as part of a multidisciplinary approach involving oncologists, surgeons, genetic counselors, and pathologists. PMID:26424758

Use of lectin microarray to differentiate gastric cancer from gastric ulcer

PubMed Central

Huang, Wei-Li; Li, Yang-Guang; Lv, Yong-Chen; Guan, Xiao-Hui; Ji, Hui-Fan; Chi, Bao-Rong

2014-01-01

AIM: To investigate the feasibility of lectin microarray for differentiating gastric cancer from gastric ulcer. METHODS: Twenty cases of human gastric cancer tissue and 20 cases of human gastric ulcer tissue were collected and processed. Protein was extracted from the frozen tissues and stored. The lectins were dissolved in buffer, and the sugar-binding specificities of lectins and the layout of the lectin microarray were summarized. The median of the effective data points for each lectin was globally normalized to the sum of medians of all effective data points for each lectin in one block. Formalin-fixed paraffin-embedded gastric cancer tissues and their corresponding gastric ulcer tissues were subjected to Ag retrieval. Biotinylated lectin was used as the primary antibody and HRP-streptavidin as the secondary antibody. The glycopatterns of glycoprotein in gastric cancer and gastric ulcer specimens were determined by lectin microarray, and then validated by lectin histochemistry. Data are presented as mean ± SD for the indicated number of independent experiments. RESULTS: The glycosylation level of gastric cancer was significantly higher than that in ulcer. In gastric cancer, most of the lectin binders showed positive signals and the intensity of the signals was stronger, whereas the opposite was the case for ulcers. Significant differences in the pathological score of the two lectins were apparent between ulcer and gastric cancer tissues using the same lectin. For MPL and VVA, all types of gastric cancer detected showed stronger staining and a higher positive rate in comparison with ulcer, especially in the case of signet ring cell carcinoma and intra-mucosal carcinoma. GalNAc bound to MPL showed a significant increase. A statistically significant association between MPL and gastric cancer was observed. As with MPL, there were significant differences in VVA staining between gastric cancer and ulcer. CONCLUSION: Lectin microarray can differentiate the different

[Investigation of gastric cancers detected at a medical check-up center].

PubMed

Kura, T; Kumaki, T; Matsuhisa, T; Tanaka, S

1996-06-01

Most of the gastric cancers investigated in this study were detected during mass screening at a Medical Check-up Center. The research period was 5 years, from 1990 to 1994. The total number of patients undergoing initial gastric examinations was 300,658. Four point eight percent of these needed detailed examinations, and 77.2% actually underwent detailed examinations. Over the 5 years, the number of gastric cancers detected was 253. The rate of detection of these cancers was almost unchanged every year, with the average rate of change being 0.11%. The rate of detected gastric cancers was investigated according to age and sex. No cancers were found below age 29, and the rate gradually rose over age 30. Over age 50, the rate in males was twice that in females. The rate of early gastric cancers was 66.4% of all reported cancers. As regards location of 253 cases, 16.5% were in the C-area, 45.8% in the M-area, 36.2% in the A-area; 19.2% were in the greater curvature, 33.9% were in the lesser curvature, 17.3% in the anterior wall, and 26.1% in the posterior wall. The sizes of the lesions were as follows: 11.5% were below 1.0 cm, 29.6% were from 1.1 cm to 2.0 cm, 46.6% were from 2.1 cm to 5.0 cm, and 12.3% were over 5.1 cm. It was considered that indirect X-rays were slightly inferior to direct X-rays in detecting early gastric cancer. The X-ray positionings in which cancers were detected were: 75.7% by supine double contrast and 48.6% by compression in 144 cases of early cancer. On the other hand, the rate were 75.6% by supine double contrast, and 51.2% by compression in 82 cases of advanced cancer. A similar tendency was found in one-shot X-ray positioning which revealed cancers. The rate of gastric cancer notdetected by X-ray pictures was 5.9% of the 253 cases. The size of the cancers notdetected by X-ray was within 2.0 cm in all cases. 58.7% of the 155 early cancer patients and 48.2% of the 83 advanced cancer patients had examinations the previous year. Therefore, it

Hypermethylation of the TSLC1 Gene Promoter in Primary Gastric Cancers and Gastric Cancer Cell Lines

PubMed Central

Honda, Teiichiro; Waki, Takayoshi; Jin, Zhe; Sato, Kiyoshi; Motoyama, Teiichi; Kawata, Sumio; Kimura, Wataru; Nishizuka, Satoshi; Murakami, Yoshinori

2002-01-01

The TSLC1 (tumor suppressor in lung cancer–1) gene is a novel tumor suppressor gene on chromosomal region 11q23.2, and is frequently inactivated by concordant promoter hypermethylation and loss of heterozygosity (LOH) in non‐small cell lung cancer (NSCLC). Because LOH on 11q has also been observed frequently in other human neoplasms including gastric cancer, we investigated the promoter methylation status of TSLC1 in 10 gastric cancer cell lines and 97 primary gastric cancers, as well as the corresponding non‐cancerous gastric tissues, by bisulfite‐SSCP analysis followed by direct sequencing. Allelic status of the TSLC1 gene was also investigated in these cell lines and primary gastric cancers. The TSLC1 promoter was methylated in two gastric cancer cell lines, KATO‐III and ECC10, and in 15 out of 97 (16%) primary gastric cancers. It was not methylated in non‐cancerous gastric tissues, suggesting that this hypermethylation is a cancer‐specific alteration. KATO‐III and ECC10 cells retained two alleles of TSLC1, both of which showed hypermethylation, associated with complete loss of gene expression. Most of the primary gastric cancers with promoter methylation also retained heterozygosity at the TSLC1 locus on 11q23.2. These data indicate that bi‐allelic hypermethylation of the TSLC1 promoter and resulting gene silencing occur in a subset of primary gastric cancers. PMID:12716461

Molecular biology of gastric cancer.

PubMed

Cervantes, A; Rodríguez Braun, E; Pérez Fidalgo, A; Chirivella González, I

2007-04-01

Despite its decreasing incidence overall, gastric cancer is still a challenging disease. Therapy is based mainly upon surgical resection when the tumour remains localised in the stomach. Conventional chemotherapy may play a role in treating micrometastatic disease and is effective as palliative therapy for recurrent or advanced disease. However, the knowledge of molecular pathways implicated in gastric cancer pathogenesis is still in its infancy and the contribution of molecular biology to the development of new targeted therapies in gastric cancer is far behind other more common cancers such as breast, colon or lung. This review will focus first on the difference of two well defined types of gastric cancer: intestinal and diffuse. A discussion of the cell of origin of gastric cancer with some intriguing data implicating bone marrow derived cells will follow, and a comprehensive review of different genetic alterations detected in gastric cancer, underlining those that may have clinical, therapeutic or prognostic implications.

Gastric metastasis from invasive lobular breast cancer, mimicking primary gastric cancer: A case report.

PubMed

Kim, Dae Hoon; Son, Seung-Myoung; Choi, Young Jin

2018-03-01

Gastric metastasis from invasive lobular breast cancer is relatively rare, commonly presented among multiple metastases, several years after primary diagnosis of breast cancer. Importantly, gastric cancer that is synchronously presented with lobular breast cancer can be misdiagnosed as primary gastric cancer; therefore, accurate differential diagnosis is required. A 39-year-old woman was visited to our hospital because of right breast mass and progressive dyspepsia. Invasive lobular carcinoma of breast was diagnosed on core needle biopsy. Gastroscopy revealed a diffuse scirrhous mass at the prepyloric antrum and diagnosed as poorly differentiated adenocarcinoma on biopsy. Synchronous double primary breast and gastric cancers were considered. Detailed pathological analysis focused on immunohistochemical studies of selected antibodies, including those of estrogen receptors, gross cystic disease fluid protein-15, and caudal-type homeobox transcription factor 2, were studied. As a result, gastric lesion was diagnosed as metastatic gastric cancer originating from breast. Right breast conserving surgery was performed, and duodenal stent was inserted under endoscopic guidance to relieve the patient's symptoms. Systemic chemotherapy with combined administration of paclitaxel and trastuzumab was initiated. Forty-one months after the diagnosis, the patient is still undergoing the same therapy. No recurrent lesion has been identified in the breast and evidence of a partial remission of gastric wall thickening has been observed on follow-up studies without new metastatic lesions. Clinical suspicion, repeat endoscopic biopsy, and detailed histological analysis, including immunohistochemistry, are necessary for diagnosis of metastatic gastric cancer from the breast.

Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer

PubMed Central

Ding, Lin; El Zaatari, Mohamad

2017-01-01

Overview Gastric cancer has been traditionally defined by the Correa paradigm as a progression of sequential pathological events that begins with chronic inflammation [1]. Infection with Helicobacter pylori (H. pylori) is the typical explanation for why the stomach becomes chronically inflamed. Acute gastric inflammation then leads to chronic gastritis, atrophy particularly of acid-secreting parietal cells, metaplasia due to mucous neck cell expansion from trans-differentiation of zymogenic cells to dysplasia and eventually carcinoma [2]. The chapter contains an overview of gastric anatomy and physiology to set the stage for signaling pathways that play a role in gastric tumorigenesis. Finally, the major known mouse models of gastric transformation are critiqued in terms of the rationale behind their generation and contribution to our understanding of human cancer subtypes. PMID:27573785

Autoimmunity and Gastric Cancer

PubMed Central

Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

2018-01-01

Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

Gene methylation in gastric cancer.

PubMed

Qu, Yiping; Dang, Siwen; Hou, Peng

2013-09-23

Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Gastric cancer stem cells in gastric carcinogenesis, progression, prevention and treatment

PubMed Central

Li, Kang; Dan, Zeng; Nie, Yu-Qiang

2014-01-01

In recent decades, the study of the mechanism of tumorigenesis has brought much progress to cancer treatment. However, cancer stem cell (CSC) theory has changed previous views of tumors, and has provided a new method for treatment of cancer. The discovery of CSCs and their characteristics have contributed to understanding the molecular mechanism of tumor genesis and development, resulting in a new effective strategy for cancer treatment. Gastric CSCs (GCSCs) are the basis for the onset of gastric cancer. They may be derived from gastric stem cells in gastric tissues, or bone marrow mesenchymal stem cells. As with other stem cells, GCSCs highly express drug-resistance genes such as aldehyde dehydrogenase and multidrug resistance, which are resistant to chemotherapy and thus form the basis of drug resistance. Many specific molecular markers such as CD44 and CD133 have been used for identification and isolation of GCSCs, diagnosis and grading of gastric cancer, and research on GCSC-targeted therapy for gastric cancer. Therefore, discussion of the recent development and advancements in GCSCs will be helpful for providing novel insight into gastric cancer treatment. PMID:24833872

Redefining early gastric cancer.

PubMed

Barreto, Savio G; Windsor, John A

2016-01-01

The problem is that current definitions of early gastric cancer allow the inclusion of regional lymph node metastases. The increasing use of endoscopic submucosal dissection to treat early gastric cancer is a concern because regional lymph nodes are not addressed. The aim of the study was thus to critically evaluate current evidence with regard to tumour-specific factors associated with lymph node metastases in "early gastric cancer" to develop a more precise definition and improve clinical management. A systematic and comprehensive search of major reference databases (MEDLINE, EMBASE, PubMed and the Cochrane Library) was undertaken using a combination of text words "early gastric cancer", "lymph node metastasis", "factors", "endoscopy", "surgery", "lymphadenectomy" "mucosa", "submucosa", "lymphovascular invasion", "differentiated", "undifferentiated" and "ulcer". All available publications that described tumour-related factors associated with lymph node metastases in early gastric cancer were included. The initial search yielded 1494 studies, of which 42 studies were included in the final analysis. Over time, the definition of early gastric cancer has broadened and the indications for endoscopic treatment have widened. The mean frequency of lymph node metastases increased on the basis of depth of infiltration (mucosa 6% vs. submucosa 28%), presence of lymphovascular invasion (absence 9% vs. presence 53%), tumour differentiation (differentiated 13% vs. undifferentiated 34%) and macroscopic type (elevated 13% vs. flat 26%) and tumour diameter (≤2 cm 8% vs. >2 cm 25%). There is a need to re-examine the diagnosis and staging of early gastric cancer to ensure that patients with one or more identifiable risk factor for lymph node metastases are not denied appropriate chemotherapy and surgical resection.

Trends and predictions for gastric cancer mortality in Brazil.

PubMed

de Souza Giusti, Angela Carolina Brandão; de Oliveira Salvador, Pétala Tuani Candido; Dos Santos, Juliano; Meira, Karina Cardoso; Camacho, Amanda Rodrigues; Guimarães, Raphael Mendonça; Souza, Dyego L B

2016-07-28

To analyze the effect of age-period and birth cohort on gastric cancer mortality, in Brazil and across its five geographic regions, by sex, in the population over 20 years of age, as well as make projections for the period 2010-2029. An ecological study is presented herein, which distributed gastric cancer-related deaths in Brazil and its geographic regions. The effects of age-period and birth cohort were calculated by the Poisson regression model and projections were made with the age-period-cohort model in the statistical program R. Progressive reduction of mortality rates was observed in the 1980's, and then higher and lower mortality rates were verified in the 2000's, for both sexes, in Brazil and for the South, Southeast and Midwest regions. A progressive decrease in mortality rates was observed for the Northeast (both sexes) and North (men only) regions within the period 1995-1999, followed by rising rates. Regional differences were demonstrated in the mortality rates for gastric cancer in Brazil, and the least developed regions of the country will present increases in projected mortality rates.

Prognostic significance of cancer family history for patients with gastric cancer: a single center experience from China.

PubMed

Liu, Xiaowen; Cai, Hong; Yu, Lin; Huang, Hua; Long, Ziwen; Wang, Yanong

2016-06-14

Family history of cancer is a risk factor for gastric cancer. In this study, we investigated the prognoses of gastric cancer patients with family history of cancer. A total of 1805 gastric cancer patients who underwent curative gastrectomy from 2000 to 2008 were evaluated. The clinicopathologic parameters and prognoses of gastric cancer patients with a positive family history (PFH) of cancer were compared with those with a negative family history (NFH). Of 1805 patients, 382 (21.2%) patients had a positive family history of cancer. Positive family history of cancer correlated with younger age, more frequent alcohol and tobacco use, worse differentiation, smaller tumor size, and more frequent tumor location in the lower 1/3 of the stomach. The prognoses of patients with a positive family history of cancer were better than that of patients with a negative family history. Family history of cancer independently correlated with better prognosis after curative gastrectomy in gastric cancer patients.

[An Analysis of Perforated Gastric Cancer with Acute Peritonitis in Our Hospital].

PubMed

Adachi, Shinichi; Endo, Shunji; Chinen, Yoshinao; Itakura, Hiroaki; Takayama, Hirotoshi; Tsuda, Yujiro; Ueda, Masami; Nakashima, Shinsuke; Ohta, Katsuya; Ikenaga, Masakazu; Yamada, Terumasa

2018-01-01

Perforated gastric cancer is relatively rare and the incidence is reported about 1% of all the cases of gastric cancer. We retrospectively analyzed the clinical data of the consecutive 12 patients with perforated gastric cancer who underwent operation in our hospital between January 2005 and December 2016. There were 5 men and 7 women, with an average age of 65.8 years old(34-87). Perforated gastric cancer occurred in the region U(1 cases), M(6 cases), L(5 cases). There were 11 cases with distant metastasis. We could successfully diagnosed as perforated gastric cancer in 8 cases before emergency operation. Gastrectomy was performed in 5 cases. However, the curative resection was performed only 1 case. Prognosis of perforated gastric cancer is poor. We considered as an appropriate two-step surgical strategy that the first step of surgery is an acute peritonitis treatment followed by radical gastrectomy with lymphadenectomy.

DBGC: A Database of Human Gastric Cancer

PubMed Central

Wang, Chao; Zhang, Jun; Cai, Mingdeng; Zhu, Zhenggang; Gu, Wenjie; Yu, Yingyan; Zhang, Xiaoyan

2015-01-01

The Database of Human Gastric Cancer (DBGC) is a comprehensive database that integrates various human gastric cancer-related data resources. Human gastric cancer-related transcriptomics projects, proteomics projects, mutations, biomarkers and drug-sensitive genes from different sources were collected and unified in this database. Moreover, epidemiological statistics of gastric cancer patients in China and clinicopathological information annotated with gastric cancer cases were also integrated into the DBGC. We believe that this database will greatly facilitate research regarding human gastric cancer in many fields. DBGC is freely available at http://bminfor.tongji.edu.cn/dbgc/index.do PMID:26566288

Gastric cancer stem cells: A novel therapeutic target

PubMed Central

Singh, Shree Ram

2013-01-01

Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

Occupation and gastric cancer

PubMed Central

Raj, A; Mayberry, J; Podas, T

2003-01-01

Gastric cancer is a cause of significant morbidity and mortality. There are several risk factors, with occupation emerging as one of these. There is considerable evidence that occupations in coal and tin mining, metal processing, particularly steel and iron, and rubber manufacturing industries lead to an increased risk of gastric cancer. Other "dusty" occupations—for example, wood processing, or work in high temperature environments have also been implicated but the evidence is not strong. The mechanism of pathogenesis of gastric cancer is unclear and the identification of causative agents can be difficult. Dust is thought to be a contributor to the pathological process, but well known carcinogens such as N-nitroso compounds have been detected in some environments. Further research on responsible agents is necessary and screening for detection of precursor gastric cancer lesions at the workplace merits consideration. PMID:12782770

Incidence trends and mortality rates of gastric cancer in Israel.

PubMed

Lavy, Ron; Kapiev, Andronik; Poluksht, Natan; Halevy, Ariel; Keinan-Boker, Lital

2013-04-01

Gastric cancer is the fourth most common malignancy worldwide. The incidence trends and mortality rates of gastric cancer in Israel have not been studied in depth. The aim of our study was to try and investigate the aforementioned issues in Israel in different ethnic groups. This retrospective study is based on the data of The Israel National Cancer Registry and The Central Bureau of Statistics. Published data from these two institutes were collected, summarized, and analyzed in this study. Around 650 new cases of gastric cancer are diagnosed yearly in Israel. While we noticed a decline during the period 1990-2007 in the incidence in the Jewish population (13.6-8.9 and 6.75-5.42 cases per 100,000 in Jewish men and women, respectively), an increase in the Arab population was noticed (7.7-10.2 and 3.7-4.2 cases per 100,000 in men and women, respectively). Age-adjusted mortality rates per 10,000 cases of gastric cancer decreased significantly, from 7.21 in 1990 to 5.46 in 2007, in the total population. The 5-year relative survival showed a slight increase for both men and women. There is a difference in the incidence and outcome of gastric cancer between the Jewish and Arab populations in Israel. The grim prognosis of gastric cancer patients in Israel is probably due to the advanced stage at which gastric cancer is diagnosed in Israel.

Is screening and surveillance for early detection of gastric cancer needed in Korean Americans?

PubMed Central

Kim, Gwang Ha; Bang, Sung Jo; Ende, Alexander R.; Hwang, Joo Ha

2015-01-01

The incidence rate of gastric cancer in Korean Americans is over five times higher than that in non-Hispanic whites, and is similar to the incidence of colorectal cancer in the overall United States population. In Korea, the National Cancer Screening Program recommends endoscopy or upper gastrointestinal series for people aged 40 years and older every 2 years. However, the benefit of gastric cancer screening in Korean Americans has not been evaluated. Based on epidemiologic studies, Korean Americans appear to have more similar gastric cancer risk factors to Koreans as opposed to Americans of European descent, though the risk of gastric cancer appears to decrease for subsequent generations. Therefore, in accordance with recent recommendations regarding screening for gastric cancer in Korea, endoscopic screening for gastric cancer in Korean Americans should be considered, especially in those with known atrophic gastritis/intestinal metaplasia or a family history of gastric cancer. In the future, additional studies will needed to assess whether a screening program for gastric cancer in Korean Americans will result in a survival benefit. PMID:26552450

Curative gastric resection for the elderly patients suffering from gastric cancer.

PubMed

Al Mansour, M; Izzo, L; Mazzone, G; Gabriele, R; Di Cello, P; Basso, L; Ranieri, E; Costi, U; Jovanovic, T; Izzo, P

2016-01-01

The improvement of the socio-economic conditions and the progress of medicine have extended the life span of the world's population and as a result, the number of patients with malignant neoplasms has increased. Gastric cancer is the third most common cancer (after lung and prostate) and the second leading cause of death caused by cancer (after lung bronchogenic cell carcinoma) in males; while it's the fifth cancer by frequency and the fourth cause of cancer death in females. It presents a peculiar geographical distribution with a lower incidence in Western Europe and North America, and higher incidence in the Far East, South America and Eastern Europe. Its incidence in Italy is 122 cases per 100000 inhabitants in males and 83 cases per 100000 inhabitants in females (in Italy). It occurs more frequently in old age, is quite rare in individuals under the age of 45. The aim of this work is to analyze the clinical and pathological characteristics of gastric carcinoma and the feasibility of curative surgery in patients over 75, identifying the factors affecting mortality, morbidity, survival and quality of life after surgery. These data have been compared with those of younger patients to assess the correct type of surgery.

Trends and predictions for gastric cancer mortality in Brazil

PubMed Central

de Souza Giusti, Angela Carolina Brandão; de Oliveira Salvador, Pétala Tuani Candido; dos Santos, Juliano; Meira, Karina Cardoso; Camacho, Amanda Rodrigues; Guimarães, Raphael Mendonça; Souza, Dyego L B

2016-01-01

AIM: To analyze the effect of age-period and birth cohort on gastric cancer mortality, in Brazil and across its five geographic regions, by sex, in the population over 20 years of age, as well as make projections for the period 2010-2029. METHODS: An ecological study is presented herein, which distributed gastric cancer-related deaths in Brazil and its geographic regions. The effects of age-period and birth cohort were calculated by the Poisson regression model and projections were made with the age-period-cohort model in the statistical program R. RESULTS: Progressive reduction of mortality rates was observed in the 1980’s, and then higher and lower mortality rates were verified in the 2000’s, for both sexes, in Brazil and for the South, Southeast and Midwest regions. A progressive decrease in mortality rates was observed for the Northeast (both sexes) and North (men only) regions within the period 1995-1999, followed by rising rates. CONCLUSION: Regional differences were demonstrated in the mortality rates for gastric cancer in Brazil, and the least developed regions of the country will present increases in projected mortality rates. PMID:27605887

Menstrual and Reproductive Factors and Risk of Gastric and Colorectal Cancer in Spain.

PubMed

Lope, Virginia; Fernández de Larrea, Nerea; Pérez-Gómez, Beatriz; Martín, Vicente; Moreno, Victor; Costas, Laura; Longo, Federico; Jiménez-Moleón, José Juan; Llorca, Javier; Ascunce, Nieves; Peiró-Pérez, Rosana; Altzibar, Jone M; Tardón, Adonina; Alguacil, Juan; Navarro, Carmen; Sierra, Ángeles; Vega, Ana Belén; Villafañe, Amaya; Castaño-Vinyals, Gemma; Kogevinas, Manolis; Pollán, Marina; Aragonés, Nuria

2016-01-01

Sex hormones play a role in gastric cancer and colorectal cancer etiology, however, epidemiological evidence is inconsistent. This study examines the influence of menstrual and reproductive factors over the risk of both tumors. In this case-control study 128 women with gastric cancer and 1293 controls, as well as 562 female and colorectal cancer cases and 1605 controls were recruited in 9 and 11 Spanish provinces, respectively. Population controls were frequency matched to cases by age and province. Demographic and reproductive data were directly surveyed by trained staff. The association with gastric, colon and rectal cancer was assessed using logistic and multinomial mixed regression models. Our results show an inverse association of age at first birth with gastric cancer risk (five-year trend: OR = 0.69; p-value = 0.006). Ever users of hormonal contraception presented a decreased risk of gastric (OR = 0.42; 95%CI = 0.26-0.69), colon (OR = 0.64; 95%CI = 0.48-0.86) and rectal cancer (OR = 0.61; 95%CI = 0.43-0.88). Postmenopausal women who used hormone replacement therapy showed a decreased risk of colon and rectal tumors. A significant interaction of educational level with parity and months of first child lactation was also observed. These findings suggest a protective role of exogenous hormones in gastric and colorectal cancer risk. The role of endogenous hormones remains unclear.

Human gastric cancer modelling using organoids.

PubMed

Seidlitz, Therese; Merker, Sebastian R; Rothe, Alexander; Zakrzewski, Falk; von Neubeck, Cläre; Grützmann, Konrad; Sommer, Ulrich; Schweitzer, Christine; Schölch, Sebastian; Uhlemann, Heike; Gaebler, Anne-Marlene; Werner, Kristin; Krause, Mechthild; Baretton, Gustavo B; Welsch, Thilo; Koo, Bon-Kyoung; Aust, Daniela E; Klink, Barbara; Weitz, Jürgen; Stange, Daniel E

2018-04-27

Gastric cancer is the second leading cause of cancer-related deaths and the fifth most common malignancy worldwide. In this study, human and mouse gastric cancer organoids were generated to model the disease and perform drug testing to delineate treatment strategies. Human gastric cancer organoid cultures were established, samples classified according to their molecular profile and their response to conventional chemotherapeutics tested. Targeted treatment was performed according to specific druggable mutations. Mouse gastric cancer organoid cultures were generated carrying molecular subtype-specific alterations. Twenty human gastric cancer organoid cultures were established and four selected for a comprehensive in-depth analysis. Organoids demonstrated divergent growth characteristics and morphologies. Immunohistochemistry showed similar characteristics to the corresponding primary tissue. A divergent response to 5-fluoruracil, oxaliplatin, irinotecan, epirubicin and docetaxel treatment was observed. Whole genome sequencing revealed a mutational spectrum that corresponded to the previously identified microsatellite instable, genomic stable and chromosomal instable subtypes of gastric cancer. The mutational landscape allowed targeted therapy with trastuzumab for ERBB2 alterations and palbociclib for CDKN2A loss. Mouse cancer organoids carrying Kras and Tp53 or Apc and Cdh1 mutations were characterised and serve as model system to study the signalling of induced pathways. We generated human and mouse gastric cancer organoids modelling typical characteristics and altered pathways of human gastric cancer. Successful interference with activated pathways demonstrates their potential usefulness as living biomarkers for therapy response testing. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of infectious complications on gastric cancer recurrence.

PubMed

Hayashi, Tsutomu; Yoshikawa, Takaki; Aoyama, Toru; Hasegawa, Shinichi; Yamada, Takanobu; Tsuchida, Kazuhito; Fujikawa, Hirohito; Sato, Tsutomu; Ogata, Takashi; Cho, Haruhiko; Oshima, Takashi; Rino, Yasushi; Masuda, Munetaka

2015-04-01

Postoperative infectious complications increase disease recurrence in colorectal cancer patients. We herein investigated the impact of infectious complications on gastric cancer recurrence after curative surgery. In total, 502 patients who underwent R0 resection for gastric cancer were reviewed. Patients were classified into those with infectious complications (IC group) and those without infectious complications (NO group). The risk factors for recurrence-free survival (RFS) were identified. Infectious complications, which occurred in 52 patients (10.4%), included pneumonia, ileus with a systemic inflammatory reaction, anastomotic leakage, and intraperitoneal abscess. The overall 5-year RFS rate was 83% in the NO group and 58% in the IC group (p = 0.000). Multivariate analysis demonstrated that age, ASA score, stage, and infectious complications were significant predictors of RFS. Infectious complications were a risk factor for gastric cancer recurrence. To avoid causing infectious complications, the surgical procedure, surgical strategy, and perioperative care should be carefully planned.

Menstrual and reproductive factors and gastric cancer risk in a large prospective study of women.

PubMed

Freedman, Neal D; Chow, Wong-Ho; Gao, Yu-Tang; Shu, Xiao-Ou; Ji, Bu-Tian; Yang, Gong; Lubin, Jay H; Li, Hong-Lan; Rothman, Nathaniel; Zheng, Wei; Abnet, Christian C

2007-12-01

Gastric cancer incidence rates are consistently lower in women than men in both high and low-risk regions worldwide. Sex hormones, such as progesterone and estrogen, may protect women against gastric cancer. To investigate the association of menstrual and reproductive factors and gastric cancer risk. These associations were prospectively investigated in 73 442 Shanghai women. After 419 260 person-years of follow-up, 154 women were diagnosed with gastric cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusted for age, body mass index, education, income, and cigarette use. No associations were observed between gastric cancer risk and age of menarche, number of children, breast feeding, or oral contraceptive use. In contrast, associations were observed with age of menopause (HR 0.80 per five-year increase in menopausal age, 95% CI 0.66-0.97), years of fertility (participants with less than 30 years of fertility were at increased risk compared with those with 30-36 years of fertility, HR 1.90, 95% CI 1.25-2.90), years since menopause (HR 1.26 per five years, 95% CI 1.03-1.53), and intrauterine device use (HR for users 1.61, 95% CI 1.08-2.39). These results support the hypothesis that female hormones play a protective role in gastric cancer risk.

The impact of old age on surgical outcomes of totally laparoscopic gastrectomy for gastric cancer.

PubMed

Kim, Min Gyu; Kim, Hee Sung; Kim, Byung Sik; Kwon, Sung Joon

2013-11-01

Old age is regarded as the risk factor of major abdominal surgery due to the lack of functional reserve and the increased presence of comorbidities. This study aimed to evaluate the impact of old age on the surgical outcomes of totally laparoscopic gastrectomy for gastric cancer. This study enrolled 389 gastric cancer patients who underwent totally laparoscopic gastrectomy at Hanyang University Guri Hospital and ASAN Medical Center. The patients were classified into two groups according to age as those older than 70 years and those younger than 70 years. Early surgical outcomes such as operation time, postoperative complications, time to first flatus, days until soft diet began, and hospital stay were evaluated. No patient was converted to open surgery. The two groups differed significantly in terms of overall postoperative complication rate, time to first flatus, days until soft diet began, and hospital stay. The patients who underwent Roux-en-Y gastrojejunostomy differed in incidence of postoperative ileus but not in severe postoperative complication rate. The results of this study demonstrated that old age can have an effect on the surgical outcomes of totally laparoscopic gastrectomy. This study especially showed that elderly patients are affected by the return of bowel movement after totally laparoscopic gastrectomy. On the other hand, however, it is presumed that old age has not had a serious impact on surgical outcomes in totally laparoscopic gastrectomy because no difference in the severe postoperative complication rate was observed.

Molecular classification of gastric cancer.

PubMed

Röcken, Christoph

2017-03-01

Gastric cancer is among the most common cancers worldwide. Despite declining incidences, the prognosis remains dismal in Western countries and is better in Asian countries with national cancer screening programs. Complete endoscopic or surgical resection of the primary tumor with or without lymphadenectomy offers the only chance of cure in the early stage of the disease. Survival of more locally advanced gastric cancers was improved by the introduction of perioperative, adjuvant and palliative chemotherapy. However, the identification and usage of novel predictive and diagnostic targets is urgently needed. Areas covered: Recent comprehensive molecular profiling of gastric cancer proposed four molecular subtypes, i.e. Epstein-Barr virus-associated, microsatellite instable, chromosomal instable and genomically stable carcinomas. The new molecular classification will spur clinical trials exploring novel targeted therapeutics. This review summarizes recent advancements of the molecular classification, and based on that, putative pitfalls for the development of tissue-based companion diagnostics, i.e. prevalence of actionable targets and therapeutic efficacy, tumor heterogeneity and tumor evolution, impact of ethnicity on gastric cancer biology, and standards of care in the East and West. Expert commentary: The overall low prevalence of actionable targets and tumor heterogeneity are the two main obstacles of precision medicine for gastric cancer.

Improving the Endoscopic Detection Rate in Patients with Early Gastric Cancer

PubMed Central

2015-01-01

Endoscopists should ideally possess both sufficient knowledge of the endoscopic gastrointestinal disease findings and an appropriate attitude. Before performing endoscopy, the endoscopist must identify several risk factors of gastric cancer, including the patient's age, comorbidities, and drug history, a family history of gastric cancer, previous endoscopic findings of atrophic gastritis or intestinal metaplasia, and a history of previous endoscopic treatments. During endoscopic examination, the macroscopic appearance is very important for the diagnosis of early gastric cancer; therefore, the endoscopist should have a consistent and organized endoscope processing technique and the ability to comprehensively investigate the entire stomach, even blind spots. PMID:26240801

Coffee intake and gastric cancer risk: the Singapore Chinese health study.

PubMed

Ainslie-Waldman, Cheryl E; Koh, Woon-Puay; Jin, Aizhen; Yeoh, Khay Guan; Zhu, Feng; Wang, Renwei; Yuan, Jian-Min; Butler, Lesley M

2014-04-01

Despite experimental evidence showing chemopreventive effects of coffee-related compounds on gastric carcinogenesis, epidemiologic studies generally do not support coffee-gastric cancer associations. Observational data are lacking among high-risk populations with sufficient regular coffee consumption. We examined the association between caffeinated coffee intake and gastric cancer risk in a population-based cohort that enrolled 63,257 Chinese men and women ages 45 to 74 years between 1993 and 1998 in Singapore. Incident gastric cancer cases (n = 647) were identified after a mean follow-up of 14.7 years. Biomarkers of Helicobacter pylori (H. pylori) infection were measured in a subset of gastric cancer cases with blood collected before cancer diagnosis and their matched controls. In the total cohort, daily versus nondaily coffee intake was associated with a statistically nonsignificant decrease in gastric cancer risk [HR = 0.85; 95% confidence interval (CI), 0.69-1.04]. In women, the inverse association strengthened and reached statistical significance (HR = 0.63; 95% CI, 0.46-0.87). In analyses restricted to never smokers and nondrinkers of alcohol, inverse associations strengthened in the total cohort (HR = 0.69; 95% CI, 0.52-0.91) and in women (HR = 0.52; 95% CI, 0.37-0.74). There was no coffee-gastric cancer risk association among men, regardless of smoking status or alcohol consumption. Similar results were observed in the nested case-control study after adjustment for H. pylori infection. Daily coffee consumption may reduce the risk of gastric cancer in high-risk populations, especially among women. Research aimed at identifying the compounds in coffee that may protect against gastric carcinogenesis is warranted.

Inflammation, atrophy, and gastric cancer

PubMed Central

Fox, James G.; Wang, Timothy C.

2006-01-01

The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world’s population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment. PMID:17200707

General Information about Gastric Cancer

MedlinePlus

... Research Gastric Cancer Treatment (PDQ®)–Patient Version General Information About Gastric Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Glucose metabolism in gastric cancer: The cutting-edge

PubMed Central

Yuan, Lian-Wen; Yamashita, Hiroharu; Seto, Yasuyuki

2016-01-01

Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer. PMID:26877609

Current approaches to gastric cancer in Peru and Mexico.

PubMed

Santos, Erlan

2017-01-01

In Peru, the incidence of gastric cancer is reported to be around 15.8 per 100,000 inhabitants and it is the second most common oncological disease in men and the third one in women. Additionally, a high mortality index was reported, especially among poor people. To address this issue, in 2008, Peru initiated several insurance treatment plans of oncological diseases with promising results. In Mexico, there is a high predominance of gastric cancer in male gender compared to female gender, even reaching a 2/1 ratio, and the detection rate of early gastric cancer is low (10% to 20%) which results in a mainly palliative treatment with an overall survival rate in 5 years about 10% to 15% only. In Peru, the average age at diagnosis is around 62.96±14.75 years old and the most frequent symptoms includes abdominal pain, indigestion, loss of appetite, weight loss and gastrointestinal bleeding, while in Mexico, some studies reported an average age at diagnosis around 60.3±4.1 years old (range, 23-78 years old) and the most frequent symptoms were postprandial fullness (74.4%), abdominal pain (37.2%), weight loss (18.6%), and melena (4.6%). The anemia rate was 65.1% with a mean Hb level of 6.14 g/dL. In Peru, the most common gastric cancer type is the intestinal-type adenocarcinoma (around 34%), followed by the diffuse-type adenocarcinoma (18.7%), whilst among Mexicans, the diffuse-type was reported in 55.2% of cases, the intestinal-type was reported in 28.2% and the undifferentiated-type corresponded to 6%. In both, Peru and Mexico, 90% of the associated factors includes tabaquismo, diets rich in salt, smoked foods, and a sedentary lifestyle. Family inheritance and advanced age and pharmacological-resistant Helicobacter pylori infection are also important. Poverty has been heavily associated with a higher incidence of gastric cancer. The management of gastric cancer patients in Peru is carried out by general surgeons or general surgical oncologists. In recent years, efforts

Molecular pathology of gastric cancer: research and practice.

PubMed

Yasui, Wataru; Sentani, Kazuhiro; Sakamoto, Naoya; Anami, Katsuhiro; Naito, Yutaka; Oue, Naohide

2011-10-15

Recent advances in the understanding of molecular stomach carcinogenesis are reviewed. As to molecular events in individual mucin phenotypes of gastric cancer, the CDX2-Reg IV-SOX9 pathway is associated with the intestinal mucin phenotype, while OLFM4 and CLDN18 are novel markers for the gastric phenotype. microRNAs play an important role in epigenetic deregulation in gastric cancer. Many microRNAs are up-regulated and down-regulated, and some of these are associated with histological differentiation and cancer progression. Reduced miR-200 may participate in the genesis of diffuse type gastric cancer by reducing E-cadherin expression. Genetic polymorphism is a crucial endogenous cause and a fundamental factor of cancer risk. PSCA polymorphism alters the susceptibility to diffuse type gastric cancer through modulation of cell proliferation activity. Cancer stem cells possess the capacity for self-renewal and cause the heterogeneous lineages of cancer cells. Cancer stem cells also show resistance to anti-tumor chemotherapy. Only a minor population of gastric cancer cells reveals the properties of cancer stem cells, and CD44 is one of the markers for gastric cancer stem cells. The origin of gastric cancer stem cells remains to be elucidated. Copyright © 2011 Elsevier GmbH. All rights reserved.

Apatinib for the treatment of gastric cancer.

PubMed

Roviello, Giandomenico; Ravelli, Andrea; Fiaschi, Anna Ida; Cappelletti, Maria Rosa; Gobbi, Angela; Senti, Chiara; Zanotti, Laura; Polom, Karol; Reynolds, Andrew R; Fox, Stephen B; Generali, Daniele

2016-08-01

Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2, has demonstrated encouraging anti-cancer activity in gastric cancer within both in vitro and in vivo models. Apatinib's efficacy, tolerability and safety have been evaluated in one Phase II and one Phase III study in metastatic/advanced gastric cancer. In this review, we focus on the mechanism of action of apatinib, its pharmacokinetic profile and its clinical activity in the treatment of advanced/metastatic gastric cancer. Expert commentary: Unfortunately, as yet, there is no definitive biomarker data for apatinib in gastric cancer.

Sensitive and specific detection of early gastric cancer with DNA methylation analysis of gastric washes.

PubMed

Watanabe, Yoshiyuki; Kim, Hyun Soo; Castoro, Ryan J; Chung, Woonbok; Estecio, Marcos R H; Kondo, Kimie; Guo, Yi; Ahmed, Saira S; Toyota, Minoru; Itoh, Fumio; Suk, Ki Tae; Cho, Mee-Yon; Shen, Lanlan; Jelinek, Jaroslav; Issa, Jean-Pierre J

2009-06-01

Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 nonneoplastic gastric mucosa samples. Six genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test, and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer, whereas PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r = 0.5-0.9, P = .03-.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the receiver operating characteristic curve (0.961) in terms of tumor detection in gastric washes. These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally, we have developed a new method for gastric cancer detection by DNA methylation in gastric washes.

Coffee intake and gastric cancer risk: The Singapore Chinese Health Study

PubMed Central

Ainslie-Waldman, Cheryl E.; Koh, Woon-Puay; Jin, Aizhen; Yeoh, Khay Guan; Zhu, Feng; Wang, Renwei; Yuan, Jian-Min; Butler, Lesley M.

2014-01-01

Background Despite experimental evidence showing chemopreventive effects of coffee-related compounds on gastric carcinogenesis, epidemiologic studies generally do not support coffee-gastric cancer associations. Observational data are lacking among high-risk populations with sufficient regular coffee consumption. Methods We examined the association between caffeinated coffee intake and gastric cancer risk in a population-based cohort that enrolled 63,257 Chinese men and women aged 45–74 years between 1993 and 1998 in Singapore. Incident gastric cancer cases (n=647) were identified after a mean follow-up of 14.7 years. Biomarkers of Helicobacter pylori (H. pylori) infection were measured in a subset of gastric cancer cases with blood collected prior to cancer diagnosis and their matched controls. Results In the total cohort, daily versus non-daily coffee intake was associated with a statistically non-significant decrease in gastric cancer risk [hazards ratio (HR) = 0.85; 95% confidence interval (CI): 0.69, 1.04). In women, the inverse association strengthened and reached statistical significance (HR=0.63; 95% CI: 0.46, 0.87). In analyses restricted to never smokers and nondrinkers of alcohol, inverse associations strengthened in the total cohort (HR=0.69; 95% CI: 0.52, 0.91) and in women (HR=0.52; 95% CI: 0.37, 0.74). There was no coffee-gastric cancer risk association among men, regardless of smoking status or alcohol consumption. Similar results were observed in the nested case-control study after adjustment for H. pylori infection. Conclusion Daily coffee consumption may reduce the risk of gastric cancer in high-risk populations, especially among women. Impact: Research aimed at identifying the compounds in coffee that may protect against gastric carcinogenesis is warranted. PMID:24608187

Helicobacter pylori Diversity and Gastric Cancer Risk

PubMed Central

2016-01-01

ABSTRACT Gastric cancer is a leading cause of cancer-related death worldwide. Helicobacter pylori infection is the strongest known risk factor for this malignancy. An important goal is to identify H. pylori-infected persons at high risk for gastric cancer, so that these individuals can be targeted for therapeutic intervention. H. pylori exhibits a high level of intraspecies genetic diversity, and over the past two decades, many studies have endeavored to identify strain-specific features of H. pylori that are linked to development of gastric cancer. One of the most prominent differences among H. pylori strains is the presence or absence of a 40-kb chromosomal region known as the cag pathogenicity island (PAI). Current evidence suggests that the risk of gastric cancer is very low among persons harboring H. pylori strains that lack the cag PAI. Among persons harboring strains that contain the cag PAI, the risk of gastric cancer is shaped by a complex interplay among multiple strain-specific bacterial factors as well as host factors. This review discusses the strain-specific properties of H. pylori that correlate with increased gastric cancer risk, focusing in particular on secreted proteins and surface-exposed proteins, and describes evidence from cell culture and animal models linking these factors to gastric cancer pathogenesis. Strain-specific features of H. pylori that may account for geographic variation in gastric cancer incidence are also discussed. PMID:26814181

Epidermal growth factor receptor mutation in gastric cancer.

PubMed

Liu, Zhimin; Liu, Lina; Li, Mei; Wang, Zhaohui; Feng, Lu; Zhang, Qiuping; Cheng, Shihua; Lu, Shen

2011-04-01

Epidermal growth factor receptor (EGFR) and Kirsten-RAS (KRAS) mutations have been identified as predictors of response to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer. We aimed to screen the mutations of both genes in gastric carcinoma to detect the suitability of EGFR TKIs for patients with gastric carcinoma. We screened EGFR mutation in exons 19-21 and KRAS mutation in exon 2 in 58 gastric adenocarcinomas from China using high resolution melting analysis (HRMA). Positive samples were confirmed by DNA sequencing. Three EGFR missense mutations (5.2%) and 22 single nucleotide polymorphisms (SNP, Q787Q, 37.9%) were identified. To our knowledge, we report for the first time three mutation patterns of EGFR, Y801C, L858R and G863D, in gastric carcinoma. Two samples with EGFR mutation were mucinous adenocarcinoma. These three samples were collected from male patients aged over 75 years old. The frequency of KRAS mutation was 10.3% (6/58). The exclusiveness of EGFR and KRAS mutations was proven for the first time in gastric cancer. Gastric carcinoma of the mucinous adenocarcinoma type collected from older male patients may harbour EGFR mutations. The small subset of gastric adenocarcinoma patients may respond to EGFR TKIs.

Sensitive and Specific Detection of Early Gastric Cancer Using DNA Methylation Analysis of Gastric Washes

PubMed Central

Watanabe, Yoshiyuki; Kim, Hyun Soo; Castoro, Ryan J.; Chung, Woonbok; Estecio, Marcos R. H.; Kondo, Kimie; Guo, Yi; Ahmed, Saira S.; Toyota, Minoru; Itoh, Fumio; Suk, Ki Tae; Cho, Mee-Yon; Shen, Lanlan; Jelinek, Jaroslav; Issa, Jean-Pierre J.

2009-01-01

Background & Aims Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. Methods We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 non-neoplastic gastric mucosa samples. Results 6 genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer while PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r=0.5 to 0.9, p=0.03 to 0.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the ROC curve (0.961) in terms of tumor detection in gastric washes. Conclusions These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally we have developed a new methodology for gastric cancer detection by DNA methylation in gastric washes. PMID:19375421

18F-fluorodeoxyglucose positron emission tomography/computed tomography findings of gastric lymphoma: Comparisons with gastric cancer.

PubMed

Wu, Jiang; Zhu, Hong; Li, Kai; Wang, Xin-Gang; Gui, Yi; Lu, Guang-Ming

2014-10-01

The role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in numerous malignant tumors, including gastric lymphoma, is well-established. However, there have been few studies with regard to the 18 F-FDG PET/CT features of gastric lymphoma. The aim of the present study was to characterize the 18 F-FDG PET/CT features of gastric lymphoma, which were compared with those of gastric cancer. Prior to treatment, 18 F-FDG PET/CT was performed on 24 patients with gastric lymphoma and 43 patients with gastric cancer. The 18 F-FDG PET/CT pattern of gastric wall lesions was classified as one of three types: Type I, diffuse thickening of the gastric wall with increased FDG uptake infiltrating more than one-third of the total stomach; type II, segmental thickening of the gastric wall with elevated FDG uptake involving less than one-third of the total stomach; and type III, local thickening of the gastric wall with focal FDG uptake. The incidence of the involvement of more than one region of the stomach was higher in the patients with gastric lymphoma than in those with gastric cancer. Gastric FDG uptake was demonstrated in 23 of the 24 patients (95.8%) with gastric lymphoma and in 40 of the 43 patients (93.0%) with gastric cancer. Gastric lymphoma predominantly presented with type I and II lesions, whereas gastric cancer mainly presented with type II and III lesions. The maximal thickness was larger and the maximal standard uptake value (SUV max ) was higher in the patients with gastric lymphoma compared with those with gastric cancer. A positive correlation between the maximal thickness and SUV max was confirmed for the gastric cancer lesions, but not for the gastric lymphoma lesions. There was no difference in the maximal thickness and SUV max of the gastric wall lesions between the patients without and with extragastric involvement, for gastric lymphoma and gastric cancer. Overall, certain differences exist in the findings between

18F-fluorodeoxyglucose positron emission tomography/computed tomography findings of gastric lymphoma: Comparisons with gastric cancer

PubMed Central

WU, JIANG; ZHU, HONG; LI, KAI; WANG, XIN-GANG; GUI, YI; LU, GUANG-MING

2014-01-01

The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in numerous malignant tumors, including gastric lymphoma, is well-established. However, there have been few studies with regard to the 18F-FDG PET/CT features of gastric lymphoma. The aim of the present study was to characterize the 18F-FDG PET/CT features of gastric lymphoma, which were compared with those of gastric cancer. Prior to treatment, 18F-FDG PET/CT was performed on 24 patients with gastric lymphoma and 43 patients with gastric cancer. The 18F-FDG PET/CT pattern of gastric wall lesions was classified as one of three types: Type I, diffuse thickening of the gastric wall with increased FDG uptake infiltrating more than one-third of the total stomach; type II, segmental thickening of the gastric wall with elevated FDG uptake involving less than one-third of the total stomach; and type III, local thickening of the gastric wall with focal FDG uptake. The incidence of the involvement of more than one region of the stomach was higher in the patients with gastric lymphoma than in those with gastric cancer. Gastric FDG uptake was demonstrated in 23 of the 24 patients (95.8%) with gastric lymphoma and in 40 of the 43 patients (93.0%) with gastric cancer. Gastric lymphoma predominantly presented with type I and II lesions, whereas gastric cancer mainly presented with type II and III lesions. The maximal thickness was larger and the maximal standard uptake value (SUVmax) was higher in the patients with gastric lymphoma compared with those with gastric cancer. A positive correlation between the maximal thickness and SUVmax was confirmed for the gastric cancer lesions, but not for the gastric lymphoma lesions. There was no difference in the maximal thickness and SUVmax of the gastric wall lesions between the patients without and with extragastric involvement, for gastric lymphoma and gastric cancer. Overall, certain differences exist in the findings between gastric

The risk of gastric cancer in carriers of CHEK2 mutations.

PubMed

Teodorczyk, Urszula; Cybulski, Cezary; Wokołorczyk, Dominika; Jakubowska, Anna; Starzyńska, Teresa; Lawniczak, Małgorzata; Domagała, Paweł; Ferenc, Katarzyna; Marlicz, Krzysztof; Banaszkiewicz, Zbigniew; Wiśniowski, Rafał; Narod, Steven A; Lubiński, Jan

2013-09-01

CHEK2 is a tumor suppressor gene whose functions are central to the induction of cell cycle arrest and apoptosis following DNA damage. Mutations in CHEK2 have been associated with cancers at many sites, including breast and prostate cancers, but the relationship between CHEK2 and gastric cancer has not been extensively studied. In Poland, there are four known founder alleles of CHEK2; three alleles are protein truncating (1100delC, IVS2G>A, del5395) and the other is a missense variant (I157T). We examined the frequencies of four Polish founder mutations in the CHEK2 gene in 658 unselected gastric cancer patients, in 154 familial gastric cancer patients and in 8,302 controls. A CHEK2 mutation was seen in 57 of 658 (8.7 %) unselected patients with gastric cancer compared to 480 of 8,302 (5.8 %) controls (OR 1.6, p = 0.004). A CHEK2 mutation was present in 19 of 154 (12.3 %) familial cases (OR = 2.3, p = 0.001). The odds ratio for early onset (<50 years) gastric cancer was higher (2.1, p = 0.01), than for cases diagnosed at age of 50 or above (OR 1.4, p = 0.05). Truncating mutations of CHEK2 were associated with higher risk (OR = 2.1, p = 0.02) than the missense mutation I157T (OR = 1.4, p = 0.04). CHEK2 mutations predispose to gastric cancer, in particular to young-onset cases.

Development and validation of a risk assessment tool for gastric cancer in a general Japanese population.

PubMed

Iida, Masahiro; Ikeda, Fumie; Hata, Jun; Hirakawa, Yoichiro; Ohara, Tomoyuki; Mukai, Naoko; Yoshida, Daigo; Yonemoto, Koji; Esaki, Motohiro; Kitazono, Takanari; Kiyohara, Yutaka; Ninomiya, Toshiharu

2018-05-01

There have been very few reports of risk score models for the development of gastric cancer. The aim of this study was to develop and validate a risk assessment tool for discerning future gastric cancer risk in Japanese. A total of 2444 subjects aged 40 years or over were followed up for 14 years from 1988 (derivation cohort), and 3204 subjects of the same age group were followed up for 5 years from 2002 (validation cohort). The weighting (risk score) of each risk factor for predicting future gastric cancer in the risk assessment tool was determined based on the coefficients of a Cox proportional hazards model in the derivation cohort. The goodness of fit of the established risk assessment tool was assessed using the c-statistic and the Hosmer-Lemeshow test in the validation cohort. During the follow-up, gastric cancer developed in 90 subjects in the derivation cohort and 35 subjects in the validation cohort. In the derivation cohort, the risk prediction model for gastric cancer was established using significant risk factors: age, sex, the combination of Helicobacter pylori antibody and pepsinogen status, hemoglobin A1c level, and smoking status. The incidence of gastric cancer increased significantly as the sum of risk scores increased (P trend < 0.001). The risk assessment tool was validated internally and showed good discrimination (c-statistic = 0.76) and calibration (Hosmer-Lemeshow test P = 0.43) in the validation cohort. We developed a risk assessment tool for gastric cancer that provides a useful guide for stratifying an individual's risk of future gastric cancer.

Relationship between Salt Preference and Gastric Cancer Screening: An Analysis of a Nationwide Survey in Korea.

PubMed

Shin, Ji-Yeon; Kim, Jeongseon; Choi, Kui Son; Suh, Mina; Park, Boyoung; Jun, Jae Kwan

2016-07-01

Epidemiological studies have demonstrated an association between excessive salt intake and gastric cancer risk, and this potential risk increases the need for adequate gastric cancer screening in individuals with high salt intake. However, the association between salt intake and gastric cancer screening in the general population has rarely been investigated. We explored the association between salt preference and participation in gastric cancer screening among a nationally representative Korean population. The study population was derived from the Korean National Cancer Screening Survey (KNCSS) 2006-2007, an annual nationwide interview survey investigating cancer screening rates. Of 4,055 individuals who participated in the KNCSS 2006-2007, 3,336 individuals aged over 40 years were included in our analysis. The odds ratio (OR) and 95% confidence interval (CI) were estimated using polytomous logistic regression. Individuals with higher salt preference were less likely to participate in regular gastric cancer screening. After adjusting for age, sex, monthly household income, education, family history of cancer, and self-rated health status, ORs for undergoing regular gastric cancer screening were 1.00, 0.82 (95% CI, 0.61 to 1.12), 0.74 (95% CI, 0.54 to 1.00), 0.77 (95% CI, 0.56 to 1.05), and 0.38 (95% CI, 0.16 to 0.92) according to the level of salt preference (p for trend=0.048). Individuals with higher salt preference showed suboptimal gastric cancer screening adherence compared to those with a lower salt preference. These findings highlight the need for better delivery of educational messages to change risk perceptions regarding gastric cancer screening practice.

Gastric tumor from metastasis of breast cancer.

PubMed

Yamamoto, D; Yoshida, H; Sumida, K; Ueyama, Y; Kanematsu, S; Shoji, T; Sueoka, N; Tanaka, K; Tsubota, Y; Kon, M

2010-09-01

Metastatic tumours of the stomach have been reported to result from various types of cancer. Among them, gastric metastasis from breast cancer has been recognised in 0.3-18% patients (1-4). Here, a rare case of metastatic gastric tumour derived from breast carcinoma is reported. Gastric endoscopy confirmed a large, friable mass (approximately 5 cm in diameter) in the upper part of the gastric body. The mass within the stomach was difficult to distinguish from primary gastric cancer, although biopsies of this lesion revealed the characteristics of adenocarcinoma. In addition, immunohistochemistry showed the positive expression of mammaglobin. Taken together, the evidence pointed to metastasis of breast cancer to the stomach. The patient was treated with hormonal therapy (letrozole), and the size of the metastasis in the stomach was markedly reduced. Therefore, a gastric metastasis from breast cancer was diagnosed successfully using immunohistochemistry and unnecessary surgery was avoided. In conclusion, although gastric metastatic tumours derived from breast carcinoma are rare, their accurate pre-operative diagnosis and appropriate systemic treatment is essential.

Systematic review: gastric cancer incidence in pernicious anaemia.

PubMed

Vannella, L; Lahner, E; Osborn, J; Annibale, B

2013-02-01

Pernicious anaemia (PA) has an increased risk for gastric cancer (GC). It is not established whether PA patients need to undergo endoscopic/histological follow-up. To provide a systematic overview of the literature on PA and the development of gastric cancer, to estimate the gastric cancer incidence-rate. According to PRISMA, we identified studies on PA patients reporting the incidence of gastric cancer. Quality of studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Meta-analysis on annual gastric cancer incidence rates was performed. Twenty-seven studies met eligibility criteria. 7 studies were of high, 6 of medium, 10 of low and 4 of very low quality. Gastric cancer incidence-rates ranged from 0% to 0.2% per person-years in 7 American, from 0% to 0.5% in 2 Asiatic, from 0% to 1.2% in 11 Northern European studies and from 0% to 0.9% in 7 studies from other European countries. The incidence-rates of gastric cancer ranged from 0% to 1.2% per person-years in studies which used gastroscopy, from 0.1% to 0.9% in those based on International Classification of Disease. Heterogeneity between studies was not statistically significant at the 5% level (Chi-squared test = 17.9, P = 0.08). The calculated pooled gastric cancer incidence-rate was 0.27% per person-years. Meta-analysis showed overall gastric cancer relative risk in PA as 6.8 (95% CI: 2.6-18.1). This systematic review shows a pooled gastric cancer incidence-rate in pernicious anaemia of 0.27% per person-years and an estimated nearly sevenfold relative risk of gastric cancer in pernicious anaemia patients. Further high quality studies are needed to confirm this higher risk. © 2012 Blackwell Publishing Ltd.

Current approaches to gastric cancer in Peru and Mexico

PubMed Central

2017-01-01

In Peru, the incidence of gastric cancer is reported to be around 15.8 per 100,000 inhabitants and it is the second most common oncological disease in men and the third one in women. Additionally, a high mortality index was reported, especially among poor people. To address this issue, in 2008, Peru initiated several insurance treatment plans of oncological diseases with promising results. In Mexico, there is a high predominance of gastric cancer in male gender compared to female gender, even reaching a 2/1 ratio, and the detection rate of early gastric cancer is low (10% to 20%) which results in a mainly palliative treatment with an overall survival rate in 5 years about 10% to 15% only. In Peru, the average age at diagnosis is around 62.96±14.75 years old and the most frequent symptoms includes abdominal pain, indigestion, loss of appetite, weight loss and gastrointestinal bleeding, while in Mexico, some studies reported an average age at diagnosis around 60.3±4.1 years old (range, 23–78 years old) and the most frequent symptoms were postprandial fullness (74.4%), abdominal pain (37.2%), weight loss (18.6%), and melena (4.6%). The anemia rate was 65.1% with a mean Hb level of 6.14 g/dL. In Peru, the most common gastric cancer type is the intestinal-type adenocarcinoma (around 34%), followed by the diffuse-type adenocarcinoma (18.7%), whilst among Mexicans, the diffuse-type was reported in 55.2% of cases, the intestinal-type was reported in 28.2% and the undifferentiated-type corresponded to 6%. In both, Peru and Mexico, 90% of the associated factors includes tabaquismo, diets rich in salt, smoked foods, and a sedentary lifestyle. Family inheritance and advanced age and pharmacological-resistant Helicobacter pylori infection are also important. Poverty has been heavily associated with a higher incidence of gastric cancer. The management of gastric cancer patients in Peru is carried out by general surgeons or general surgical oncologists. In recent years

Survival Analysis of Patients with Interval Cancer Undergoing Gastric Cancer Screening by Endoscopy

PubMed Central

Hamashima, Chisato; Shabana, Michiko; Okamoto, Mikizo; Osaki, Yoneatsu; Kishimoto, Takuji

2015-01-01

Aims Interval cancer is a key factor that influences the effectiveness of a cancer screening program. To evaluate the impact of interval cancer on the effectiveness of endoscopic screening, the survival rates of patients with interval cancer were analyzed. Methods We performed gastric cancer-specific and all-causes survival analyses of patients with screen-detected cancer and patients with interval cancer in the endoscopic screening group and radiographic screening group using the Kaplan-Meier method. Since the screening interval was 1 year, interval cancer was defined as gastric cancer detected within 1 year after a negative result. A Cox proportional hazards model was used to investigate the risk factors associated with gastric cancer-specific and all-causes death. Results A total of 1,493 gastric cancer patients (endoscopic screening group: n = 347; radiographic screening group: n = 166; outpatient group: n = 980) were identified from the Tottori Cancer Registry from 2001 to 2008. The gastric cancer-specific survival rates were higher in the endoscopic screening group than in the radiographic screening group and the outpatients group. In the endoscopic screening group, the gastric cancer-specific survival rate of the patients with screen-detected cancer and the patients with interval cancer were nearly equal (P = 0.869). In the radiographic screening group, the gastric cancer-specific survival rate of the patients with screen-detected cancer was higher than that of the patients with interval cancer (P = 0.009). For gastric cancer-specific death, the hazard ratio of interval cancer in the endoscopic screening group was 0.216 for gastric cancer death (95%CI: 0.054-0.868) compared with the outpatient group. Conclusion The survival rate and the risk of gastric cancer death among the patients with screen-detected cancer and patients with interval cancer were not significantly different in the annual endoscopic screening. These results suggest the potential of

64Cu DOTA-Trastuzumab PET/CT in Studying Patients With Gastric Cancer

ClinicalTrials.gov

2017-12-11

Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IA Gastric Cancer; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

Gastric cancer in Gwynedd. Possible links with bracken.

PubMed Central

Galpin, O. P.; Whitaker, C. J.; Whitaker, R.; Kassab, J. Y.

1990-01-01

One hundred and one histologically confirmed gastric cancer patients in Gwynedd, North Wales, were matched by sex, age and social class to two hospital inpatients without cancer. Seventy-seven of the gastric cancer cases were also matched, using the same criteria, to a patient with a confirmed cancer of a different site (excluding oesophagus). A questionnaire was used to determine bracken exposure and source of water in childhood. Residential and occupational histories were obtained and the consumption of buttermilk, a potential vector of the bracken carcinogens, was quantified. Comparison of the gastric cancer patients with the non-cancer controls indicated that exposure to bracken in childhood had an increased risk (RR = 2.34, P less than 0.001) compared to no exposure and that length of residence in Gwynedd was associated with increased risk (RR = 2.46 for durations of 61 years and over, P less than 0.01). Consumption of buttermilk in childhood and adulthood was attended by increased risk (RR = 1.61 and 1.86 respectively, the latter being statistically significant, P less than 0.05). Neither the residence effect nor consumption of buttermilk in adulthood remained significant when considered in a multivariate analysis with bracken exposure. PMID:2337510

The remarkable geographical pattern of gastric cancer mortality in Ecuador.

PubMed

Montero-Oleas, Nadia; Núñez-González, Solange; Simancas-Racines, Daniel

2017-12-01

This study was aimed to describe the gastric cancer mortality trend, and to analyze the spatial distribution of gastric cancer mortality in Ecuador, between 2004 and 2015. Data were collected from the National Institute of Statistics and Census (INEC) database. Crude gastric cancer mortality rates, standardized mortality ratios (SMRs) and indirect standardized mortality rates (ISMRs) were calculated per 100,000 persons. For time trend analysis, joinpoint regression was used. The annual percentage rate change (APC) and the average annual percent change (AAPC) was computed for each province. Spatial age-adjusted analysis was used to detect high risk clusters of gastric cancer mortality, from 2010 to 2015, using Kulldorff spatial scan statistics. In Ecuador, between 2004 and 2015, gastric cancer caused a total of 19,115 deaths: 10,679 in men and 8436 in women. When crude rates were analyzed, a significant decline was detected (AAPC: -1.8%; p<0.001). ISMR also decreased, but this change was not statistically significant (APC: -0.53%; p=0.36). From 2004 to 2007 and from 2008 to 2011 the province with the highest ISMR was Carchi; and, from 2012 to 2015, was Cotopaxi. The most likely high occurrence cluster included Bolívar, Los Ríos, Chimborazo, Tungurahua, and Cotopaxi provinces, with a relative risk of 1.34 (p<0.001). There is a substantial geographic variation in gastric cancer mortality rates among Ecuadorian provinces. The spatial analysis indicates the presence of high occurrence clusters throughout the Andes Mountains. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Molecular classification of gastric cancer: a new paradigm.

PubMed

Shah, Manish A; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y; Klimstra, David S; Gerdes, Hans; Kelsen, David P

2011-05-01

Gastric cancer may be subdivided into 3 distinct subtypes--proximal, diffuse, and distal gastric cancer--based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (National Cancer Institute, NCI #5917) underwent endoscopic biopsy for fresh tumor procurement. Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection was carried out to ensure more than 80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the 3 gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross-validation error was 0.14, suggesting that more than 85% of samples were classified correctly. Gene set analysis with the false discovery rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Subtypes of gastric cancer that have epidemiologic and histologic distinctions are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. ©2011 AACR.

Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms.

PubMed

Kim, Young Beak; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

2016-03-01

Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma.

Epstein–Barr Virus Infection and Gastric Cancer

PubMed Central

Chen, Xin-Zu; Chen, Hongda; Castro, Felipe A.; Hu, Jian-Kun; Brenner, Hermann

2015-01-01

Abstract Epstein–Barr virus (EBV) infection is found in a subset of gastric cancers. Previous reviews have exclusively focused on EBV-encoded small RNA (EBER) positivity in gastric cancer tissues, but a comprehensive evaluation of other type of studies is lacking. We searched the PubMed database up to September, 2014, and performed a systematic review. We considered studies comparing EBV nucleic acids positivity in gastric cancer tissue with positivity in either adjacent non-tumor tissue of cancer patients or non-tumor mucosa from healthy individuals, patients with benign gastric diseases, or deceased individuals. We also considered studies comparing EBV antibodies in serum from cancer patients and healthy controls. Selection of potentially eligible studies and data extraction were performed by 2 independent reviewers. Due to the heterogeneity of studies, we did not perform formal meta-analysis. Forty-seven studies (8069 cases and 1840 controls) were identified. EBER positivity determined by in situ hybridization (ISH) was significantly higher in cancer tissues (range 5.0%–17.9%) than in adjacent mucosa from the same patients or biopsies from all control groups (almost 0%). High EBV nuclear antigen-1 (EBNA-1) positivity by PCR was found in gastric cancer tissues, but most were not validated by ISH or adjusted for inflammatory severity and lymphocyte infiltration. Only 4 studies tested for EBV antibodies, with large variation in the seropositivities of different antibodies in both cases and controls, and did not find an association between EBV seropositivity and gastric cancer. In summary, tissue-based ISH methods strongly suggest an association between EBV infection and gastric cancer, but PCR method alone is invalid to confirm such association. Very limited evidence from serological studies and the lack of novel antibodies warrant further investigations to identify potential risk factors of EBV for gastric cancer. PMID:25997049

Estrogen receptors in gastric cancer: Advances and perspectives.

PubMed

Ur Rahman, Muhammad Saif; Cao, Jiang

2016-02-28

Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of the development and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future

Telomerase activity in gastric cancer.

PubMed

Hiyama, E; Yokoyama, T; Tatsumoto, N; Hiyama, K; Imamura, Y; Murakami, Y; Kodama, T; Piatyszek, M A; Shay, J W; Matsuura, Y

1995-08-01

Although many genetic alterations have been reported in gastric cancer, it is not known whether all gastric tumors are capable of indefinite proliferative potential, e.g., immortality. The expression of telomerase and stabilization of telomeres are concomitant with the attainment of immortality in tumor cells; thus, the measurement of telomerase activity in clinically obtained tumor samples may provide important information useful both as a diagnostic marker to detect immortal cancer cells in clinical materials and as a prognostic indicator of patient outcome. Telomerase activity was analyzed in 66 primary gastric cancers with the use of a PCR-based assay. The majority of tumors (85%) displayed telomerase activity, but telomerase was undetectable in 10 tumors (15%), 8 of which were early stage tumors. Most of the tumors with telomerase activity were large and of advanced stages, including metastases. Survival rate of patients of tumors with detectable telomerase activity was significantly shorter than that of those without telomerase activity. Alterations of telomere length (reduced/elongated terminal restriction fragments) were detected in 14 of 66 (21%) gastric cancers, and all 14 had telomerase activity. Cellular DNA contents revealed that all 22 aneuploid tumors had detectable telomerase activity. The present results indicate that telomerase activation may be required as a critical step in the multigenetic process of tumorigenesis, and that telomerase is frequently but not always activated as a late event in gastric cancer progression.

TPX2 expression is associated with poor survival in gastric cancer.

PubMed

Tomii, Chiharu; Inokuchi, Mikito; Takagi, Yoko; Ishikawa, Toshiaki; Otsuki, Sho; Uetake, Hiroyuki; Kojima, Kazuyuki; Kawano, Tatsuyuki

2017-01-09

Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for microtubule formation in human cells. Several studies have demonstrated that TPX2 is overexpressed in multiple tumor types and promotes tumor growth and metastasis. However, there have been few reports regarding its role in gastric cancer. In this study, we evaluated TPX2 expression and investigated its correlations with gastric cancer clinicopathological features and prognosis. Tumor samples were obtained from 290 patients with gastric adenocarcinoma who had undergone gastrectomy. The expression of TPX2 protein was examined using immunohistochemical staining. TPX2 messenger RNA (mRNA) levels were evaluated using real-time quantitative reverse transcription PCR in 19 of the gastric cancer tumors and adjacent normal tissues. The mRNA levels of TPX2 were significantly higher in gastric cancer tissues than in matched adjacent normal tissues (p = 0.004). In the immunohistochemical analysis, TPX2 overexpression was found in 123 (42.4%) of 290 patients. High TPX2 expression was positively associated with age, type of histology, depth of tumor, lymph node metastasis, stage, and remote metastasis or recurrence. High TPX2 expression was significantly associated with poorer disease-specific survival (p = 0.004) and relapse-free interval (p = 0.013). Our results indicated that high TPX2 expression was associated with tumor progression and poor survival in gastric cancer.

Current issues and future perspectives of gastric cancer screening

PubMed Central

Hamashima, Chisato

2014-01-01

Gastric cancer remains the second leading cause of cancer death worldwide. About half of the incidence of gastric cancer is observed in East Asian countries, which show a higher mortality than other countries. The effectiveness of 3 new gastric cancer screening techniques, namely, upper gastrointestinal endoscopy, serological testing, and “screen and treat” method were extensively reviewed. Moreover, the phases of development for cancer screening were analyzed on the basis of the biomarker development road map. Several observational studies have reported the effectiveness of endoscopic screening in reducing mortality from gastric cancer. On the other hand, serologic testing has mainly been used for targeting the high-risk group for gastric cancer. To date, the effectiveness of new techniques for gastric cancer screening has remained limited. However, endoscopic screening is presently in the last trial phase of development before their introduction to population-based screening. To effectively introduce new techniques for gastric cancer screening in a community, incidence and mortality reduction from gastric cancer must be initially and thoroughly evaluated by conducting reliable studies. In addition to effectiveness evaluation, the balance of benefits and harms must be carefully assessed before introducing these new techniques for population-based screening. PMID:25320514

Gastric cancer research in Mexico: a public health priority.

PubMed

Sampieri, Clara Luz; Mora, Mauricio

2014-04-28

This study aimed review studies conducted on Mexican patients diagnosed with gastric cancer and/or diseases associated with its development, in which at least one Mexican institute has participated, and to assess their contributions to the primary and secondary prevention of this disease. A search of the Medline database was conducted using the following keywords: gastric/stomach cancer, Mexico. Studies of the Mexican population were selected in which at least one Mexican Institute had participated and where the findings could support public policy proposals directed towards the primary or secondary prevention of gastric cancer. Of the 148 studies found in the Medline database, 100 were discarded and 48 were reviewed. According to the analysis presented, these studies were classified as: epidemiology of gastric cancer (5/48); risk factors and protectors relating to gastric cancer (9/48); relationship between Helicobacter pylori and pathologies associated with gastric cancer and the development of the disease (16/48); relationship between the Epstein-Barr virus and pathologies associated with gastric cancer and the development of the disease (3/48); molecular markers for the development of diseases associated with gastric cancer and gastric cancer (15/48). Mexico requires a program for the prevention and control of gastric cancer based on national health indicators. This should be produced by a multidisciplinary committee of experts who can propose actions that are relevant in the current national context. The few studies of gastric cancer conducted on the Mexican population in national institutes highlight the poor connection that currently exists between the scientific community and the health sector in terms of resolving this health issue. Public policies for health research should support projects with findings that can be translated into benefits for the population. This review serves to identify national research groups studying gastric cancer in the Mexican

Gastric cancer research in Mexico: A public health priority

PubMed Central

Sampieri, Clara Luz; Mora, Mauricio

2014-01-01

This study aimed review studies conducted on Mexican patients diagnosed with gastric cancer and/or diseases associated with its development, in which at least one Mexican institute has participated, and to assess their contributions to the primary and secondary prevention of this disease. A search of the Medline database was conducted using the following keywords: gastric/stomach cancer, Mexico. Studies of the Mexican population were selected in which at least one Mexican Institute had participated and where the findings could support public policy proposals directed towards the primary or secondary prevention of gastric cancer. Of the 148 studies found in the Medline database, 100 were discarded and 48 were reviewed. According to the analysis presented, these studies were classified as: epidemiology of gastric cancer (5/48); risk factors and protectors relating to gastric cancer (9/48); relationship between Helicobacter pylori and pathologies associated with gastric cancer and the development of the disease (16/48); relationship between the Epstein-Barr virus and pathologies associated with gastric cancer and the development of the disease (3/48); molecular markers for the development of diseases associated with gastric cancer and gastric cancer (15/48). Mexico requires a program for the prevention and control of gastric cancer based on national health indicators. This should be produced by a multidisciplinary committee of experts who can propose actions that are relevant in the current national context. The few studies of gastric cancer conducted on the Mexican population in national institutes highlight the poor connection that currently exists between the scientific community and the health sector in terms of resolving this health issue. Public policies for health research should support projects with findings that can be translated into benefits for the population. This review serves to identify national research groups studying gastric cancer in the Mexican

Family history of gastric cancer is associated with the risk of colorectal neoplasia in Korean population.

PubMed

Jung, Yoon Suk; Kim, Nam Hee; Yang, Hyo-Joon; Park, Soo-Kyung; Park, Jung Ho; Park, Dong Il; Sohn, Chong Il

2017-10-01

Family history of cancers at different sites except for colorectum has not been evaluated as a risk factor for colorectal neoplasia (CRN). To investigate CRN risk according to family history of cancers at 12 different sites, including stomach and colorectum. A cross-sectional study was performed on 139,497 asymptomatic Koreans who underwent colonoscopy as part of a health check-up. The mean age of the study population was 41.6 and the prevalence of CRN was 16.3%. Multivariate analyses revealed that family histories of CRC (adjusted odds ratio; confidence interval, 1.26; 1.17-1.35) and gastric cancer (1.07; 1.01-1.13) were independent risk factors for CRN. Notably, the risk of CRN increased even more for participants with family histories of both CRC and gastric cancer (1.38; 1.12-1.70). Family history of CRC was associated with risk of CRN in participants aged both <50 and ≥50 years, whereas family history of gastric cancer was associated with risk of CRN in participants aged <50 years (1.22; 1.14-1.30), but not in participants aged ≥50 years (1.08; 0.99-1.18). Family history of gastric cancer was an independent risk factor for CRN, especially in those aged <50years. Persons with family histories of gastric cancer and CRC, especially those with family histories of both, may need to begin colonoscopy earlier. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Prognostic significance of aberrant gene methylation in gastric cancer.

PubMed

Shi, Jing; Zhang, Guanjun; Yao, Demao; Liu, Wei; Wang, Na; Ji, Meiju; He, Nongyue; Shi, Bingyin; Hou, Peng

2012-01-01

Promoter methylation acts as an important alternative to genetic alterations for gene inactivation in gastric carcinogenesis. Although a number of gastric cancer-associated genes have been found to be methylated in gastric cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. In the present study, we used methylation-specific PCR (MSP) to analyze promoter methylation of 9 gastric cancer-associated genes, including MLF1, MGMT, p16, RASSF2, hMLH1, HAND1, HRASLS, TM, and FLNc, and their association with clinicopathological characteristics and clinical outcome in a large cohort of gastric cancers. Our data showed that all of these genes were aberrantly methylated in gastric cancer, ranging from 8% to 51%. Moreover, gene methylation was strongly associated with certain clinicopathological characteristics, such as tumor differentiation, lymph node metastasis, and cancer-related death. Of interest, methylation of MGMT, p16, RASSF2, hMLH1, HAND1, and FLNc was closely associated with poor survival in gastric cancer, particularly MGMT, p16, RASSF2 and FLNc. Thus, our findings suggested these epigenetic events may contribute to the initiation and progression of gastric cancer. Importantly, methylation of some genes were closely relevant to poor prognosis in gastric cancer, providing the strong evidences that these hypermethylated genes may be served as valuable biomarkers for prognostic evaluation in this cancer.

Prognostic significance of aberrant gene methylation in gastric cancer

PubMed Central

Shi, Jing; Zhang, Guanjun; Yao, Demao; Liu, Wei; Wang, Na; Ji, Meiju; He, Nongyue; Shi, Bingyin; Hou, Peng

2012-01-01

Promoter methylation acts as an important alternative to genetic alterations for gene inactivation in gastric carcinogenesis. Although a number of gastric cancer-associated genes have been found to be methylated in gastric cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. In the present study, we used methylation-specific PCR (MSP) to analyze promoter methylation of 9 gastric cancer-associated genes, including MLF1, MGMT, p16, RASSF2, hMLH1, HAND1, HRASLS, TM, and FLNc, and their association with clinicopathological characteristics and clinical outcome in a large cohort of gastric cancers. Our data showed that all of these genes were aberrantly methylated in gastric cancer, ranging from 8% to 51%. Moreover, gene methylation was strongly associated with certain clinicopathological characteristics, such as tumor differentiation, lymph node metastasis, and cancer-related death. Of interest, methylation of MGMT, p16, RASSF2, hMLH1, HAND1, and FLNc was closely associated with poor survival in gastric cancer, particularly MGMT, p16, RASSF2 and FLNc. Thus, our findings suggested these epigenetic events may contribute to the initiation and progression of gastric cancer. Importantly, methylation of some genes were closely relevant to poor prognosis in gastric cancer, providing the strong evidences that these hypermethylated genes may be served as valuable biomarkers for prognostic evaluation in this cancer. PMID:22206050

Multi-disciplinary team for early gastric cancer diagnosis improves the detection rate of early gastric cancer.

PubMed

Di, Lianjun; Wu, Huichao; Zhu, Rong; Li, Youfeng; Wu, Xinglong; Xie, Rui; Li, Hongping; Wang, Haibo; Zhang, Hua; Xiao, Hong; Chen, Hui; Zhen, Hong; Zhao, Kui; Yang, Xuefeng; Xie, Ming; Tuo, Bigung

2017-12-06

Gastric cancer is a frequent malignant tumor worldwide and its early detection is crucial for curing the disease and enhancing patients' survival rate. This study aimed to assess whether the multi-disciplinary team (MDT) can improve the detection rate of early gastric cancer (EGC). The detection rate of EGC at the Digestive Endoscopy Center, Affiliated Hospital, Zunyi Medical College, China between September 2013 and September 2015 was analyzed. MDT for the diagnosis of EGC in the hospital was established in September 2014. The study was divided into 2 time periods: September 1, 2013 to August 31, 2014 (period 1) and September 1, 2014 to September 1, 2015 (period 2). A total of 60,800 patients' gastroscopies were performed during the two years. 61 of these patients (0.1%) were diagnosed as EGC, accounting for 16.44% (61/371) of total patients with gastric cancer. The EGC detection rate before MDT (period 1) was 0.05% (16/29403), accounting for 9.09% (16/176) of total patients with gastric cancer during this period. In comparison, the EGC detection rate during MDT (period 2) was 0.15% (45/31397), accounting for 23% (45/195) of total patients with gastric cancer during this period (P < 0.05). Univariate and multivariate logistic analyses showed that intensive gastroscopy for high risk patients of gastric cancer enhanced the detection rate of EGC in cooperation with Department of Pathology (OR = 10.1, 95% CI 2.39-43.3, P < 0.05). MDT could improve the endoscopic detection rate of EGC.

Pathogenesis of Gastric Cancer: Genetics and Molecular Classification.

PubMed

Figueiredo, Ceu; Camargo, M C; Leite, Marina; Fuentes-Pananá, Ezequiel M; Rabkin, Charles S; Machado, José C

Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.

Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms

PubMed Central

Kim, Young Beak; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

2016-01-01

Background/Aims Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. Methods Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. Results In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). Conclusions The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma. PMID:26087787

Metaplasia in the Stomach—Precursor of Gastric Cancer?

PubMed Central

Kinoshita, Hiroto; Koike, Kazuhiko

2017-01-01

Despite a significant decrease in the incidence of gastric cancer in Western countries over the past century, gastric cancer is still one of the leading causes of cancer-related deaths worldwide. Most human gastric cancers develop after long-term Helicobacter pylori infection via the Correa pathway: the progression is from gastritis, atrophy, intestinal metaplasia, dysplasia, to cancer. However, it remains unclear whether metaplasia is a direct precursor of gastric cancer or merely a marker of high cancer risk. Here, we review human studies on the relationship between metaplasia and cancer in the stomach, data from mouse models of metaplasia regarding the mechanism of metaplasia development, and the cellular responses induced by H. pylori infection. PMID:28953255

Metaplasia in the Stomach-Precursor of Gastric Cancer?

PubMed

Kinoshita, Hiroto; Hayakawa, Yoku; Koike, Kazuhiko

2017-09-27

Despite a significant decrease in the incidence of gastric cancer in Western countries over the past century, gastric cancer is still one of the leading causes of cancer-related deaths worldwide. Most human gastric cancers develop after long-term Helicobacter pylori infection via the Correa pathway: the progression is from gastritis, atrophy, intestinal metaplasia, dysplasia, to cancer. However, it remains unclear whether metaplasia is a direct precursor of gastric cancer or merely a marker of high cancer risk. Here, we review human studies on the relationship between metaplasia and cancer in the stomach, data from mouse models of metaplasia regarding the mechanism of metaplasia development, and the cellular responses induced by H. pylori infection.

Prognostic value of tumor size in gastric cancer: an analysis of 2,379 patients.

PubMed

Guo, Pengtao; Li, Yangming; Zhu, Zhi; Sun, Zhe; Lu, Chong; Wang, Zhenning; Xu, Huimian

2013-04-01

Tumor size has been included into the staging systems of many solid tumors, such as lung and breast. However, tumor size is not integrated in the staging of gastric cancer, and its prognostic value for gastric cancer needs to be reappraised. A total of 2,379 patients who received radical resection for histopathologically confirmed gastric adenocarcinoma were enrolled in the present study. Tumor size, originally presented as continuous variable, was categorized into small gastric cancer (SGC) group and large gastric cancer (LGC) group using an optimal cutoff point determined by Cox proportional hazards model. The associations between tumor size and other clinicopathological factors were checked using Chi-square test. Survival of gastric cancer patients was estimated by using univariate Kaplan-Meier method, and the survival difference was checked by using the log-rank test. The significant clinicopathological factors were included into the Cox proportional hazards model to determine the independent prognostic factors, and their hazard ratios were calculated. With the optimal cutoff point of 4 cm, tumor size was categorized into SGC group (≤ 4 cm) and LGC group (>4 cm). Tumor size closely correlated with age, tumor location, macroscopic type, Lauren classification, and lymphatic vessel invasion. Moreover, tumor size was also significantly associated with depth of tumor invasion and status of regional lymph nodes. The 5-year survival rate was 68.7 % for SGC group which was much higher than 40.2 % for LGC group. Univariate analysis showed that SGC had a better survival than LGC, mainly for patients with IIA, IIB, and IIIA stage. Multivariate analysis revealed that tumor size as well as age, tumor location, macroscopic type, Lauren classification, lymphatic vessel invasion, depth of tumor invasion, and status of regional lymph nodes were independent prognostic factors for gastric cancer. Tumor size is a reliable prognostic factor for patients with gastric cancer, and

Glycoprofiling of Early Gastric Cancer Using Lectin Microarray Technology.

PubMed

Li, Taijie; Mo, Cuiju; Qin, Xue; Li, Shan; Liu, Yinkun; Liu, Zhiming

2018-01-01

Recently, studies have reported that protein glycosylation plays an important role in the occurrence and development of cancer. Gastric cancer is a common cancer with high morbidity and mortality owing to most gastric cancers are discovered only at an advanced stage. Here, we aim to discover novel specific serum glycanbased biomarkers for gastric cancer. A lectin microarray with 50 kinds of tumor-associated lectin was used to detect the glycan profiles of serum samples between early gastric cancer and healthy controls. Then lectin blot was performed to validate the differences. The result of the lectin microarray showed that the signal intensities of 13 lectins showed significant differences between the healthy controls and early gastric cancer. Compared to the healthy, the normalized fluorescent intensities of the lectins PWA, LEL, and STL were significantly increased, and it implied that their specifically recognized GlcNAc showed an especially elevated expression in early gastric cancer. Moreover, the binding affinity of the lectins EEL, RCA-II, RCA-I, VAL, DSA, PHA-L, UEA, and CAL were higher in the early gastric cancer than in healthy controls. These glycan structures containing GalNAc, terminal Galβ 1-4 GlcNAc, Tri/tetraantennary N-glycan, β-1, 6GlcNAc branching structure, α-linked fucose residues, and Tn antigen were elevated in gastric cancer. While the two lectins CFL GNL reduced their binding ability. In addition, their specifically recognized N-acetyl-D-galactosamine structure and (α-1,3) mannose residues were decreased in early gastric cancer. Furthermore, lectin blot results of LEL, STL, PHA-L, RCA-I were consistent with the results of the lectin microarray. The findings of our study clarify the specific alterations for glycosylation during the pathogenesis of gastric cancer. The specific high expression of GlcNAc structure may act as a potential early diagnostic marker for gastric cancer.

Association of Helicobacter pylori infection with gastric cancer.

PubMed

Alexander, G A; Brawley, O W

2000-01-01

Helicobacter pylori has generated public health interest since its identification in 1983. Past studies have suggested that the bacterium plays a role in the pathogenesis of gastric cancer. More recent studies support the conclusion that the association of H. pylori with gastric cancer is causal. The purpose of this article is to review the available evidence supporting the association of H. pylori with gastric cancer. We performed a critical review of the relevant literature published in the English language on H. pylori and gastric cancer using MEDLINE, Index Medicus for the years 1985 to 1997. The reference lists of selected articles also were reviewed to capture citations for further pertinent studies. H. pylori is thought to be the major cause of chronic atrophic gastritis. H. pylori gastritis is worldwide in distribution. H. pylori is now categorized by the International Agency for Cancer Research as a group 1 carcinogen, i.e., an agent that is carcinogenic to humans. Several reports from the United States have found the highest frequencies of gastric cancer in geographic areas and populations with the highest rates of acquisition of H. pylori infection. The high prevalence of H. pylori infection has been documented most notably in blacks and Hispanics, who also are at high risk for gastric cancer. New studies that focus on the epidemiology and pathology of H. pylori improve our understanding of its relationship with gastric cancer and advance the development of gastric cancer prevention and control strategies that are proposed.

Salty Food Preference and Intake and Risk of Gastric Cancer: The JACC Study.

PubMed

Umesawa, Mitsumasa; Iso, Hiroyasu; Fujino, Yoshihisa; Kikuchi, Shogo; Tamakoshi, Akiko

2016-01-01

High sodium intake is a potential risk factor of gastric cancer. However, limited information is available on the relationship between salty food preference or intake and risk of gastric cancer. The aim of the present study was to determine the association between these variables among the Japanese population. Between 1988 and 1990, 15,732 men and 24,997 women aged 40-79 years old with no history of cancer or cardiovascular disease completed a lifestyle questionnaire that included information about food intake. The subjects were enrolled in the Japan Collaborative Cohort (JACC) Study for Evaluation of Cancer Risk Sponsored by Monbusho. After a median follow-up of 14.3 years, 787 incident gastric cancers were documented. We examined the associations between salty food preference and intake and gastric cancer incidence using the Cox proportional hazard model. The risk of gastric cancer among subjects with a strong preference for salty food was approximately 30% higher than among those who preferred normal-level salty food (hazard ratio [HR] 1.31; 95% confidence interval [CI], 1.02-1.67). The risk of gastric cancer in subjects who consumed 3 and ≥ 4 bowls/day of miso soup was approximately 60% higher than in those who consumed less miso soup (HR 1.67; 95% CI, 1.16-2.39 and HR 1.64; 95% CI, 1.11-2.42, respectively). Sodium intake correlated positively and linearly with risk of gastric cancer (P for trend = 0.002). The present study showed that salty food preference, consumption of large quantities of miso soup, and high sodium intake were associated with increased risk of gastric cancer among Japanese people.

Updates on esophageal and gastric cancers.

PubMed

Gallo, Amy; Cha, Charles

2006-05-28

Esophageal and gastric cancers are both common and deadly. Patients present most often after disease progression and survival is therefore poor. Due to demographic variability and recent changes in disease incidence, much emphasis has been placed on studying risk factors for both esophageal and gastric cancers. However, with increasing understanding of these diseases, low survival rates persist and continued intensive studies are necessary to optimize treatment plans. This review article discusses updates in the evolving epidemiology, clinical presentation, risk factors, and diagnostic and treatment modalities of esophageal and gastric cancers.

Molecular Classification of Gastric Cancer: A new paradigm

PubMed Central

Shah, Manish A.; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y.; Klimstra, David S.; Gerdes, Hans; Kelsen, David P.

2011-01-01

Purpose Gastric cancer may be subdivided into three distinct subtypes –proximal, diffuse, and distal gastric cancer– based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Experimental Design Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (NCI 5917) underwent endoscopic biopsy for fresh tumor procurement. 4–6 targeted biopsies of the primary tumor were obtained. Macrodissection was performed to ensure >80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Results Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the three gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross validation error was 0.14, suggesting that >85% of samples were classified correctly. Gene set analysis with the False Discovery Rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Conclusions Subtypes of gastric cancer that have epidemiologic and histologic distinction are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. PMID:21430069

[Endoscopic and pathological characteristics of gastric cancer in a Peruvian public hospital].

PubMed

Parillo Durand, Lilian Brenda

2017-01-01

The endoscopic and pathological characteristics of gastric cancer in Luis N. Sáenz National Hospital between 2008 and 2013. retrospective cross-sectional observational study. We reviewed the endoscopic reports of patients older than 30 years, we studied the histological diagnosis of gastric adenocarcinoma, pathological variables such as histological type, presence of H. pylori and complete and incomplete intestinal metaplasia. 92 cases of gastric adenocarcinoma were identified. Average prevalence 0.6%, 0.34% in 2009 and 0.82% in 2013; 62% male, 38% female, age less than 55 years 16%, greater than 76 years 42%; endoscopic presentation Borrmann III 57%, II 16.3%, IV 15%, V 7.6%, I 3.3%; 8 times most frequent presentations distal the proximal v, 75% histologic intestinal type, H. pylori in 50% cases, intestinal metaplasia in 40% of cases of gastric cancer. We found high prevalence of gastric cancer. Common in males, and in people over 76, more frequent endoscopic presentation was Borrmann III, the presence of H. pylori and incomplete intestinal metaplasia associated with intestinal cancer type.

Identifying and targeting cancer stem cells in the treatment of gastric cancer.

PubMed

Bekaii-Saab, Tanios; El-Rayes, Bassel

2017-04-15

Current treatment regimens for gastric cancer are not adequate. Cancer stem cells (CSCs) may be a key driving factor for growth and metastasis of this tumor type. In contrast to the conventional clonal evolution hypothesis, CSCs can initiate tumor formation, self-renew, and differentiate into tumor-propagating cells. Because gastric cancer can originate from CSCs, it is necessary to review current targets of signaling pathways for CSCs in gastric cancer that are being studied in clinical trials. These pathways are known to regulate the self-renewal and differentiation process in gastric CSCs. A better understanding of the clinical results of trials that target gastric CSCs will lead to better outcomes for patients with gastric cancer. Cancer 2017;123:1303-1312. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Changing strategies for target therapy in gastric cancer.

PubMed

Lee, Suk-Young; Oh, Sang Cheul

2016-01-21

In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer.

IKKε and TBK1 expression in gastric cancer.

PubMed

Lee, Seung Eun; Hong, Mineui; Cho, Junhun; Lee, Jeeyun; Kim, Kyoung-Mee

2017-03-07

Inhibitor of kappa B kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IKKs. IKKε and TBK1 share the kinase domain and are similar in their ability to activate the nuclear factor-kappa B signaling pathway. IKKε and TBK1 are overexpressed through multiple mechanisms in various human cancers. However, the expression of IKKε and TBK1 in gastric cancer and their role in prognosis have not been studied.To investigate overexpression of the IKKε and TBK1 proteins in gastric cancer and their relationship with clinicopathologic factors, we performed immunohistochemical staining using a tissue microarray. Tissue microarray samples were obtained from 1,107 gastric cancer patients who underwent R0 gastrectomy with extensive lymph node dissection and adjuvant chemotherapy.We identified expression of IKKε in 150 (13.6%) and TBK1 in 38 (3.4%) gastric cancers. Furthermore, co-expression of IKKε and TBK1 was identified in 1.5% of cases. Co-expression of IKKε and TBK1 was associated with differentiated intestinal histology and earlier T stage. In a multivariate binary logistic regression model, intestinal histologic type by Lauren classification and early AJCC stage were significant predictors for expression of IKKε and TBK1 proteins in gastric cancer. Changes in IKKε and TBK1 expression may be involved in the development of intestinal-type gastric cancer. The overexpression of IKKε and TBK1 should be considered in selected patients with intestinal-type gastric cancer.In conclusion, this is the first large-scale study investigating the relationships between expression of IKKε and TBK1 and clinicopathologic features of gastric cancer. The role of IKKε and TBK1 in intestinal-type gastric cancer pathogenesis should be elucidated by further investigation.

Risk prediction for early-onset gastric carcinoma: a case-control study of polygenic gastric cancer in Han Chinese with hereditary background.

PubMed

Yuan, Jiajia; Li, Yanyan; Tian, Tiantian; Li, Na; Zhu, Yan; Zou, Jianling; Gao, Jing; Shen, Lin

2016-06-07

Recent genomewide studies have identified several germline variations associated with gastric cancer. The aim of the present study was to identify, in a Chinese Han population, the individual and combined effects of those single nucleotide polymorphisms (SNPs) that increase the risk of early-onset gastric cancer. We conducted a case-control study comprising 116 patients with gastric cancer as well as 102 sex- and age-matched controls and confirmed that the SNPs MUC1 (mucin 1) rs9841504 and ZBTB20 (zinc finger and BTB domain containing 20) rs4072037 were associated with an increased gastric cancer risk. Of the 116 patients diagnosed with cancer, 65 had at least 1 direct lineal relative with carcinoma of the digestive system or breast/ovarian cancer. These 65 had another 4 SNPs associated with gastric cancer susceptibility: PSCA (prostate stem cell antigen) rs2294008, PLCE1 (phospholipase C epsilon 1) rs2274223, PTGER4/PRKAA1 (prostaglandin E receptor 4/ protein kinase AMP-activated catalytic subunit alpha 1) rs13361707, and TYMS (thymidylate synthetase) rs2790. However, each of these low-penetrance susceptibility polymorphisms alone is not considered influential enough to predict the absolute risk of early-onset gastric cancer. Thus we decided to study different combinations of polygenes as they affected for our population. Those subjects with both the risk alleles MUC1 rs9841504 and ZBTB20 rs4072037 had a greater than 3-fold increased risk of gastric cancer. Also those with a hereditary background including the risk alleles PLCE1 rs2274223 and PTGER4/PRKAA1 rs13361707 were 3 times more susceptible to cardia cancer than those without. These findings show that the study of combined polymorphisms, instead of single low-penetrance variations in susceptibility, may lead to a high-risk classification for a specific population.

Risk prediction for early-onset gastric carcinoma: a case-control study of polygenic gastric cancer in Han Chinese with hereditary background

PubMed Central

Yuan, Jiajia; Li, Yanyan; Tian, Tiantian; Li, Na; Zhu, Yan; Zou, Jianling; Gao, Jing; Shen, Lin

2016-01-01

Recent genomewide studies have identified several germline variations associated with gastric cancer. The aim of the present study was to identify, in a Chinese Han population, the individual and combined effects of those single nucleotide polymorphisms (SNPs) that increase the risk of early-onset gastric cancer. We conducted a case-control study comprising 116 patients with gastric cancer as well as 102 sex- and age-matched controls and confirmed that the SNPs MUC1 (mucin 1) rs9841504 and ZBTB20 (zinc finger and BTB domain containing 20) rs4072037 were associated with an increased gastric cancer risk. Of the 116 patients diagnosed with cancer, 65 had at least 1 direct lineal relative with carcinoma of the digestive system or breast/ovarian cancer. These 65 had another 4 SNPs associated with gastric cancer susceptibility: PSCA (prostate stem cell antigen) rs2294008, PLCE1 (phospholipase C epsilon 1) rs2274223, PTGER4/PRKAA1 (prostaglandin E receptor 4/protein kinase AMP-activated catalytic subunit alpha 1) rs13361707, and TYMS (thymidylate synthetase) rs2790. However, each of these low-penetrance susceptibility polymorphisms alone is not considered influential enough to predict the absolute risk of early-onset gastric cancer. Thus we decided to study different combinations of polygenes as they affected for our population. Those subjects with both the risk alleles MUC1 rs9841504 and ZBTB20 rs4072037 had a greater than 3-fold increased risk of gastric cancer. Also those with a hereditary background including the risk alleles PLCE1 rs2274223 and PTGER4/PRKAA1 rs13361707 were 3 times more susceptible to cardia cancer than those without. These findings show that the study of combined polymorphisms, instead of single low-penetrance variations in susceptibility, may lead to a high-risk classification for a specific population. PMID:27127881

Postoperative fever predicts poor prognosis of gastric cancer.

PubMed

Feng, Fan; Tian, Yangzi; Yang, Xuewen; Sun, Li; Hong, Liu; Yang, Jianjun; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

2017-09-22

Data about prognostic value of postoperative fever in gastric cancer was lacking. Thus, the present study aims to investigate the prognostic value of postoperative fever in gastric cancer. From September 2008 to March 2015, 2938 gastric cancer patients were enrolled in the present study. Clinicopathological features were recoded. The association between postoperative fever and prognosis of gastric cancer were analyzed. There were 2294 male (78.1%) and 644 female (21.9%). Seven hundred and fifty-six patients suffered from fever. Among them, the duration of fever less than 48h occurred in 508 cases, and duration of fever over 48h occurred in 248 cases. Univariate and multivariate analysis showed that postoperative fever was an independent risk factor for prognosis of gastric cancer ( P < 0.001). For the entire cohort, duration of fever over 48h was significantly associated with decreased survival ( P < 0.001). In subgroup analysis, duration of fever over 48h was significantly associated with poor prognosis of stage I and II gastric cancer (both P < 0.001). However, postoperative fever was not associated with the prognosis of stage III gastric cancer ( P = 0.334). Considering the type of gastrectomy, postoperative fever was not associated with the prognosis of patients with proximal ( P = 0.318) and distal gastrectomy ( P = 0.806), but duration of fever over 48h was significantly associated with poor prognosis of patients with total gastrectomy ( P = 0.004). In conclusion, postoperative fever was associated with poor prognosis of gastric cancer.

SIRT3 Enhances Glycolysis and Proliferation in SIRT3-Expressing Gastric Cancer Cells

PubMed Central

Cui, Yang; Qin, Lili; Wu, Jing; Qu, Xuan; Hou, Chen; Sun, Wenyan; Li, Shiyong; Vaughan, Andrew T. M.; Li, Jian Jian; Liu, Jiankang

2015-01-01

SIRT3 is a key NAD+-dependent protein deacetylase in the mitochondria of mammalian cells, functioning to prevent cell aging and transformation via regulation of mitochondrial metabolic homeostasis. However, SIRT3 is also found to express in some human tumors; its role in these SIRT3-expressing tumor cells needs to be elucidated. This study demonstrated that the expression of SIRT3 was elevated in a group of gastric cancer cells compared to normal gastric epithelial cells. Although SIRT3 expression levels were increased in the gastric tumor tissues compared to the adjacent non-tumor tissues, SIRT3 positive cancer cells were more frequently detected in the intestinal type gastric cancers than the diffuse type gastric cancers, indicating that SIRT3 is linked with subtypes of gastric cancer. Overexpression of SIRT3 promoted cell proliferation and enhanced ATP generation, glucose uptake, glycogen formation, MnSOD activity and lactate production, which were inhibited by SIRT3 knockdown, indicating that SIRT3 plays a role in reprogramming the bioenergetics in gastric tumor cells. Further analysis revealed that SIRT3 interacted with and deacetylated the lactate dehydrogenase A (LDHA), a key protein in regulating anaerobic glycolysis, enhancing LDHA activity. In consistence, a cluster of glycolysis-associated genes was upregulated in the SIRT3-overexpressing gastric tumor cells. Thus, in addition to the well-documented SIRT3-mediated mitochondrial homeostasis in normal cells, SIRT3 may enhance glycolysis and cell proliferation in SIRT3-expressing cancer cells. PMID:26121691

Impact of endoscopic screening on mortality reduction from gastric cancer

PubMed Central

Hamashima, Chisato; Ogoshi, Kazuei; Narisawa, Rintarou; Kishi, Tomoki; Kato, Toshiyuki; Fujita, Kazutaka; Sano, Masatoshi; Tsukioka, Satoshi

2015-01-01

AIM: To investigate mortality reduction from gastric cancer based on the results of endoscopic screening. METHODS: The study population consisted of participants of gastric cancer screening by endoscopy, regular radiography, and photofluorography at Niigata city in 2005. The observed numbers of cumulative deaths from gastric cancers and other cancers were accumulated by linkage with the Niigata Prefectural Cancer Registry. The standardized mortality ratio (SMR) of gastric cancer and other cancer deaths in each screening group was calculated by applying the mortality rate of the reference population. RESULTS: Based on the results calculated from the mortality rate of the population of Niigata city, the SMRs of gastric cancer death were 0.43 (95%CI: 0.30-0.57) for the endoscopic screening group, 0.68 (95%CI: 0.55-0.79) for the regular radiographic screening group, and 0.85 (95%CI: 0.71-0.94) for the photofluorography screening group. The mortality reduction from gastric cancer was higher in the endoscopic screening group than in the regular radiographic screening group despite the nearly equal mortality rates of all cancers except gastric cancer. CONCLUSION: The 57% mortality reduction from gastric cancer might indicate the effectiveness of endoscopic screening for gastric cancer. Further studies and prudent interpretation of results are needed. PMID:25741155

Prevalence of deleterious ATM germline mutations in gastric cancer patients.

PubMed

Huang, Dong-Sheng; Tao, Hou-Quan; He, Xu-Jun; Long, Ming; Yu, Sheng; Xia, Ying-Jie; Wei, Zhang; Xiong, Zikai; Jones, Sian; He, Yiping; Yan, Hai; Wang, Xiaoyue

2015-12-01

Besides CDH1, few hereditary gastric cancer predisposition genes have been previously reported. In this study, we discovered two germline ATM mutations (p.Y1203fs and p.N1223S) in a Chinese family with a history of gastric cancer by screening 83 cancer susceptibility genes. Using a published exome sequencing dataset, we found deleterious germline mutations of ATM in 2.7% of 335 gastric cancer patients of different ethnic origins. The frequency of deleterious ATM mutations in gastric cancer patients is significantly higher than that in general population (p=0.0000435), suggesting an association of ATM mutations with gastric cancer predisposition. We also observed biallelic inactivation of ATM in tumors of two gastric cancer patients. Further evaluation of ATM mutations in hereditary gastric cancer will facilitate genetic testing and risk assessment.

[Significance of CEA in gastric and colorectal cancer].

PubMed

Uehara, K; Miyamoto, Y; Izuo, M; Shiozaki, H; Aiba, S; Matsumoto, H

1985-04-01

The determination of serum CEA (Sandwich method) and CEA staining (PAP method) of excised specimens were performed in patients with gastric or colorectal cancer, and the biological characteristics of each cancer and the factors to increase serum CEA were studied with the following results: As colonic cancer has strong CEA productivity, serum CEA can be useful for the detection of cancer, and especially effective for the postoperative observation. Gastric cancer has weak CEA productivity, and serum CEA is not so useful in the detection of cancer and the judgement of resectability. The CEA positive rate of tissue with CEA staining was 80% in gastric cancer, 100% in colonic cancer, and were nearly equal to the CEA positive rate of serum in the group of terminal stage. In the mode of CEA staining of cancerous cells, IV type was observed most frequently in gastric cancer, and I type in colonic cancer. Among the resected cases showing more than 7ng/ml serum CEA, differentiated type, lymph node metastasis (+), the degree of tissue staining with CEA staining, the mode of cell staining O or I type in gastric cancer and I type in colonic cancer were observed in common.

Predicting the probability of mortality of gastric cancer patients using decision tree.

PubMed

Mohammadzadeh, F; Noorkojuri, H; Pourhoseingholi, M A; Saadat, S; Baghestani, A R

2015-06-01

Gastric cancer is the fourth most common cancer worldwide. This reason motivated us to investigate and introduce gastric cancer risk factors utilizing statistical methods. The aim of this study was to identify the most important factors influencing the mortality of patients who suffer from gastric cancer disease and to introduce a classification approach according to decision tree model for predicting the probability of mortality from this disease. Data on 216 patients with gastric cancer, who were registered in Taleghani hospital in Tehran,Iran, were analyzed. At first, patients were divided into two groups: the dead and alive. Then, to fit decision tree model to our data, we randomly selected 20% of dataset to the test sample and remaining dataset considered as the training sample. Finally, the validity of the model examined with sensitivity, specificity, diagnosis accuracy and the area under the receiver operating characteristic curve. The CART version 6.0 and SPSS version 19.0 softwares were used for the analysis of the data. Diabetes, ethnicity, tobacco, tumor size, surgery, pathologic stage, age at diagnosis, exposure to chemical weapons and alcohol consumption were determined as effective factors on mortality of gastric cancer. The sensitivity, specificity and accuracy of decision tree were 0.72, 0.75 and 0.74 respectively. The indices of sensitivity, specificity and accuracy represented that the decision tree model has acceptable accuracy to prediction the probability of mortality in gastric cancer patients. So a simple decision tree consisted of factors affecting on mortality of gastric cancer may help clinicians as a reliable and practical tool to predict the probability of mortality in these patients.

Lauren classification and individualized chemotherapy in gastric cancer.

PubMed

Ma, Junli; Shen, Hong; Kapesa, Linda; Zeng, Shan

2016-05-01

Gastric cancer is one of the most common malignancies worldwide. During the last 50 years, the histological classification of gastric carcinoma has been largely based on Lauren's criteria, in which gastric cancer is classified into two major histological subtypes, namely intestinal type and diffuse type adenocarcinoma. This classification was introduced in 1965, and remains currently widely accepted and employed, since it constitutes a simple and robust classification approach. The two histological subtypes of gastric cancer proposed by the Lauren classification exhibit a number of distinct clinical and molecular characteristics, including histogenesis, cell differentiation, epidemiology, etiology, carcinogenesis, biological behaviors and prognosis. Gastric cancer exhibits varied sensitivity to chemotherapy drugs and significant heterogeneity; therefore, the disease may be a target for individualized therapy. The Lauren classification may provide the basis for individualized treatment for advanced gastric cancer, which is increasingly gaining attention in the scientific field. However, few studies have investigated individualized treatment that is guided by pathological classification. The aim of the current review is to analyze the two major histological subtypes of gastric cancer, as proposed by the Lauren classification, and to discuss the implications of this for personalized chemotherapy.

History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer

PubMed Central

Graham, David Y

2014-01-01

Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20th century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19th century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for “surgical disease” or for “Sippy” diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori

History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer.

PubMed

Graham, David Y

2014-05-14

Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20th century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19th century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20th century physician's believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for "surgical disease" or for "Sippy" diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori-related diseases.

Effectiveness of gastric cancer screening programs in South Korea: Organized vs opportunistic models

PubMed Central

Kim, Beom Jin; Heo, Chae; Kim, Byoung Kwon; Kim, Jae Yeol; Kim, Jae Gyu

2013-01-01

AIM: To investigate the outcome and effectiveness of two screening programs, National Cancer Screening Program (NCSP) and opportunistic screening (OS), for the detection of gastric cancer. METHODS: A total of 45  654 subjects underwent upper endoscopy as part of the NCSP or OS at the Chung-Ang University Healthcare System in Korea between January 2007 and December 2010. The study population was comprised of subjects over the age of 40 years. More specifically, subjects who took part in the NCSP were Medicaid recipients and beneficiaries of the National Health Insurance Corporation. Still photographs from the endoscopies diagnosed as gastric cancer were reviewed by two experienced endoscopists. RESULTS: The mean age of the screened subjects was 55 years for men and 54 years for women. A total of 126 cases (0.28%) of gastric cancer were detected from both screening programs; 100 cases (0.3%) from NCSP and in 26 cases (0.2%) from OS. The proportion of early gastric cancer (EGC) detected in NCSP was higher than that in OS (74.0% vs 53.8%, P = 0.046). Among the 34  416 screenees in NCSP, 6585 (19.1%) underwent upper endoscopy every other year as scheduled. Among the 11  238 screenees in OS, 3050 (27.1%) underwent upper endoscopy at least once every two years during the study period. The detection rate of gastric cancer was found to be significantly higher during irregular follow-up than during regular follow-up in both screening programs (0.3% vs 0.2%, P = 0.036). A higher incidence of EGC than advanced gastric cancer was observed during regular follow-up compared with irregular follow-up. CONCLUSION: Compliance to the screening program is more important than the type of screening system used. PMID:23430471

Metastatic gastric carcinoma from breast cancer mimicking primary linitis plastica: A case report.

PubMed

Yagi, Yasumichi; Sasaki, Shozo; Yoshikawa, Akemi; Tsukioka, Yuji; Fukushima, Wataru; Fujimura, Takashi; Hirosawa, Hisashi; Izumi, Ryohei; Saito, Katsuhiko

2015-12-01

Metastases to the gastrointestinal tract rarely occur in breast cancer except in invasive lobular carcinoma. The present study reports a rare case of metastatic gastric cancer from invasive ductal carcinoma (IDC) of the breast mimicking primary gastric linitis plastica. A 51-year-old premenopausal female, who had a history of partial mastectomy for right breast cancer at the age of 40, was referred to Toyama City Hospital (Toyoma, Japan) for an endoscopic diagnosis of gastric linitis plastica. Abdominal computed tomography (CT) revealed left hydronephrosis, while peritoneal metastasis and malignant ascites were not detected. Chest CT detected a left lung tumor, which had invaded the left upper bronchus. Biopsy specimens were obtained and the histopathological findings on both the gastric tumor and lung tumor demonstrated poorly differentiated adenocarcinoma, whereas the histology of the original breast cancer was IDC with a solid-tubular type. Immunohistochemistry revealed that the biopsied specimens of the gastric and lung tumors were positive for estrogen receptor (ER), progesterone receptor (PgR) and negative for human epithelial growth factor receptor-2 (HER2). These molecular characteristics indicated the case was metastatic gastric carcinoma from the breast cancer with lung metastasis, since the statuses of ER, PgR and HER2 were concordant with those of the original breast cancer. However, the possibility of primary gastric cancer could not be completely ruled out. Therefore, a total gastrectomy was performed for the purpose of both diagnosis and treatment. Pathological examination of the resected specimen provided a definite diagnosis of multiple metastatic gastric carcinomas from the breast. To the best of our knowledge, metastatic gastric cancer derived from the breast presenting as linitis plastica 11 years following the surgical removal of IDC has not been described previously.

Apatinib for the treatment of gastric cancer.

PubMed

Geng, Ruixuan; Li, Jin

2015-01-01

Antiangiogenesis therapy plays an important role in cancer treatment. Apatinib mesylate, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, has been recommended as third-line treatment for metastatic gastric cancer patients. The current review summarizes the publications and conference reports relating to apatinib from preclinical and clinical research in gastric cancer. Apatinib showed good safety, tolerance and treatment efficacy in Phase I/II studies. In a Phase III study, apatinib prolonged the median overall survival of patients with chemotherapy-refractory metastatic gastric cancer by 55 days and the median progression-free survival by 25 days compared with placebo. Apatinib is a new treatment option for advanced gastric cancer. Apatinib is expected to have a broader application when it has been evaluated worldwide. The key issues are to find biomarkers and overcome drug resistance.

Insights into next developments in advanced gastric cancer.

PubMed

Obermannová, Radka; Lordick, Florian

2016-07-01

The purpose of the review is to delineate novel approaches for biology-based treatment in advanced gastric cancer. We reviewed the latest translational and clinical research articles and congress presentations. A new molecular classification of gastric cancer based on histology, genetic and proteomic alterations has evolved. It provides a roadmap for development of new drugs and combinations and for patient stratification. Anti-HER2 treatment, which is an effective strategy in metastatic gastric cancer, is now also being studied in the perioperative setting. However, resistance mechanisms in advanced disease are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is an emerging concept in the management of advanced gastric cancer, and ramucirumab has prolonged survival in the second line either as a monotherapy or in combination with paclitaxel. Biomarkers for selecting patients who benefit from ramucirumab are still lacking. Immune checkpoint blockade and inhibition of cancer stemness targets are other emerging directions for the medical treatment of gastric cancer. Large-scale international studies are ongoing. Promising biology-based treatment strategies are evolving. But tumor heterogeneity which is an inherent feature of gastric cancer challenges the development of molecularly targeted and personalized treatment strategies.

Advances of Molecular Targeted Therapy in Gastric Cancer.

PubMed

Cetin, Bulent; Gumusay, Ozge; Cengiz, Mustafa; Ozet, Ahmet

2016-06-01

Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life. In the treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances.

The current situation for gastric cancer in Chile

PubMed Central

Caglevic, Christian; Silva, Shirley; Mahave, Mauricio; Rolfo, Christian; Gallardo, Jorge

2016-01-01

Gastric cancer is a neoplasm with a high incidence and mortality rate in Chile where more than 3000 people die every year from this type of cancer. This study shows the clinical and epidemiological considerations of this disease, information about translational research on this pathology in Chile, the contribution of Chilean doctors to the development of gastric cancer management awareness and the general situation of gastric cancer in Chile. PMID:28105078

The current situation for gastric cancer in Chile.

PubMed

Caglevic, Christian; Silva, Shirley; Mahave, Mauricio; Rolfo, Christian; Gallardo, Jorge

2016-01-01

Gastric cancer is a neoplasm with a high incidence and mortality rate in Chile where more than 3000 people die every year from this type of cancer. This study shows the clinical and epidemiological considerations of this disease, information about translational research on this pathology in Chile, the contribution of Chilean doctors to the development of gastric cancer management awareness and the general situation of gastric cancer in Chile.

Risks for respiratory and gastric cancer in wood-working occupations in Denmark.

PubMed

Olsen, J H; Møller, H; Jensen, O M

1988-01-01

Cases of cancer notified to the Danish Cancer Registry during the period 1970 to 1984 in the age groups 16 to 66 years have been linked to information on employment kept on file in the nationwide Supplementary Pension Fund since 1964. Industrial hygienists classified industrial groups as defined by the Pension Fund with regard to exposure to wood dust, and a list of industries with major exposure to wood dust was defined. The risk for cancer of the respiratory system and the gastrointestinal tract was evaluated by means of a proportional cancer incidence analysis. A fourfold increase in risk for sinonasal cancer was found among men involved in the manufacture of wooden furniture, and a twofold increase in risk for gastric cancer was seen in all of the component industries of basic wood-processing. In contrast, no excess of gastric cancer could be detected in men working in the manufacture of wooden building materials and wooden furniture, and a risk below unity was seen for those in carpentry and joinery. The elevated risk for gastric cancer in some wood-processing industries is probably due to social factors also common to men in agriculture and manufacturing. The absence of an increased risk for gastric cancer in trades in which a high risk for sinonasal cancer is seen indicates that wood dust is not of aetiological importance for gastric cancer. No excess of total lung cancer or of the adenocarcinoma subtype was seen in any of the wood-processing industries.

Gastric adenocarcinoma in common variable immunodeficiency: features of cancer and associated gastritis may be characteristic of the condition.

PubMed

De Petris, Giovanni; Dhungel, Bal M; Chen, Longwen; Chang, Yu-Hui H

2014-10-01

Common variable immunodeficiency (CVID) is associated with an increased risk of gastric cancer. The aim of the study was to determine the morphological features of CVID-associated gastric adenocarcinoma (CAGA) and of the background gastritis. The population of gastric cancer patients with CVID of Mayo Clinic in the period 2000-2010 was studied; 6 cases of CVID (2 males, 4 females, average age 47 years, age range 26-71 years) were found in 5793 patients with gastric cancer in the study period. Each patient underwent gastric resection for which histology slides were reviewed. Chronic gastritis variables, CVID-related findings, and features of the adenocarcinoma were recorded. CAGA was of intestinal type, with high number of intratumoral lymphocytes (ITLs). Cancer was diagnosed in younger patients than in the overall population of gastric cancer. Severe atrophic metaplastic pangastritis with extensive dysplasia was present in the background in 4 cases, with features of lymphocytic gastritis in 2 cases. Features of CVID (plasma cells paucity in 4 of 6 cases, lymphoid nodules prominent in four cases) could be detected. In summary, gastric adenocarcinoma at young age with ITLs, accompanied by atrophic metaplastic pangastritis, should alert the pathologist of the possibility of CAGA. It follows that, in presence of those characteristics, the search of CVID-associated abnormalities should be undertaken in the nonneoplastic tissues. © The Author(s) 2014.

IkappaBalpha polymorphism at promoter region (rs2233408) influences the susceptibility of gastric cancer in Chinese.

PubMed

Wang, Shiyan; Tian, Linwei; Zeng, Zhirong; Zhang, Mingdong; Wu, Kaichun; Chen, Minhu; Fan, Daiming; Hu, Pinjin; Sung, Joseph J Y; Yu, Jun

2010-02-05

Nuclear factor of kappa B inhibitor alpha (I kappaB alpha) protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of I kappaB alpha to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients. A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 564 gastric cancer patients and 566 healthy controls were enrolled in this study. rs2233408 genotypes in I kappaB alpha were analyzed by TaqMan SNP genotyping assay. Both rs2233408 T homozygote (TT) and T heterozygotes (TC and TT) had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069-0.909, P = 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, P = 0.037), compared with rs2233408 C homozygote (CC). rs2233408 T heterozygotes were significantly associated with reduced risk of intestinal-type gastric cancer with ORs of 0.648 (95% CI = 0.459-0.916, P = 0.014), but not with the diffuse or mix type of gastric cancer. The association between rs2233408 T heterozygotes and gastric cancer appeared more apparent in the older patients (age>40) (OR = 0.674, 95% CI = 0.484-0.939, P = 0.02). rs2233408 T heterozygotes was associated with non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, P = 0.006), but not with cardiac gastric cancer. However, rs2233408 polymorphism was not associated with the prognosis of gastric cancer patients. I kappaB alpha rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population.

Identifying module biomarkers from gastric cancer by differential correlation network

PubMed Central

Liu, Xiaoping; Chang, Xiao

2016-01-01

Gastric cancer (stomach cancer) is a severe disease caused by dysregulation of many functionally correlated genes or pathways instead of the mutation of individual genes. Systematic identification of gastric cancer biomarkers can provide insights into the mechanisms underlying this deadly disease and help in the development of new drugs. In this paper, we present a novel network-based approach to predict module biomarkers of gastric cancer that can effectively distinguish the disease from normal samples. Specifically, by assuming that gastric cancer has mainly resulted from dysfunction of biomolecular networks rather than individual genes in an organism, the genes in the module biomarkers are potentially related to gastric cancer. Finally, we identified a module biomarker with 27 genes, and by comparing the module biomarker with known gastric cancer biomarkers, we found that our module biomarker exhibited a greater ability to diagnose the samples with gastric cancer. PMID:27703371

Robot-assisted laparoscopic gastrectomy for gastric cancer

PubMed Central

Caruso, Stefano; Franceschini, Franco; Patriti, Alberto; Roviello, Franco; Annecchiarico, Mario; Ceccarelli, Graziano; Coratti, Andrea

2017-01-01

Phase III evidence in the shape of a series of randomized controlled trials and meta-analyses has shown that laparoscopic gastrectomy is safe and gives better short-term results with respect to the traditional open technique for early-stage gastric cancer. In fact, in the East laparoscopic gastrectomy has become routine for early-stage gastric cancer. In contrast, the treatment of advanced gastric cancer through a minimally invasive way is still a debated issue, mostly due to worries about its oncological efficacy and the difficulty of carrying out an extended lymphadenectomy and intestinal reconstruction after total gastrectomy laparoscopically. Over the last ten years the introduction of robotic surgery has implied overcoming some intrinsic drawbacks found to be present in the conventional laparoscopic procedure. Robot-assisted gastrectomy with D2 lymphadenectomy has been shown to be safe and feasible for the treatment of gastric cancer patients. But unfortunately, most available studies investigating the robotic gastrectomy for gastric cancer compared to laparoscopic and open technique are so far retrospective and there have not been phase III trials. In the present review we looked at scientific evidence available today regarding the new high-tech surgical robotic approach, and we attempted to bring to light the real advantages of robot-assisted gastrectomy compared to the traditional laparoscopic and open technique for the treatment of gastric cancer. PMID:28101302

Long-term trends and survival analysis of esophageal and gastric cancer in Yangzhong, 1991-2013.

PubMed

Hua, Zhaolai; Zheng, Xianzhi; Xue, Hengchuan; Wang, Jianming; Yao, Jun

2017-01-01

To describe the long-term trends of the incidence, mortality and survival of upper digestive tract cancers in a high-risk area of China. We extracted esophageal and gastric cancer cases diagnosed from 1991 to 2013 through the Yangzhong Cancer Registry and calculated the crude and age-standardized incidence and mortality rates. Cancer trends were calculated using the Joinpoint Regression Program and were reported using the annual percentage change (APC). The cancer-specific survival rates were evaluated and compared between groups using the Kaplan-Meier method and log-rank test. The age-standardized incidence rate of esophageal cancer declined from 107.06 per 100,000 person-years (male: 118.05 per 100,000 person-years; female: 97.42 per 100,000 person-years) in 1991 to 37.04 per 100,000 person-years (male: 46.43 per 100,000 person-years; female: 27.26 per 100,000 person-years) in 2013, with an APC of -2.5% (95% confidence interval (CI): -3.4%, -1.5%) for males and -4.9% (95% CI:-5.8%, -3.9%) for females. The age-standardized incidence rate of gastric cancer was 165.11 per 100,000 person-years (male: 225.39 per 100,000 person-years; female: 113.34 per 100,000 person-years) in 1991 and 53.46 per 100,000 person-years (male: 76.51 per 100,000 person-years; female: 32.43 per 100,000 person-years) in 2013, with the APC of -3.6% (95% CI: -4.5%, -2.7%) for males and -4.8% (95% CI: -5.7%, -3.9%) for females. The median survival time was 3.0 years for patients with esophageal or gastric cancer. Cancer cases detected after 2004 had a better prognosis. The age-standardized incidence rates of both esophageal and gastric cancer continuously decreased since 1991 through 2013, whereas the mortality rate remained stable before 2004 and significantly declined following the massive endoscopic screening program initiated in 2004. The survival probability of patients with esophageal and gastric cancer has improved obviously in recent decades.

[Immunohistochemical assessment of HER2 expression in gastric cancer. A clinicopathologic study of 93 cases].

PubMed

Alvarado-Cabrero, Isabel; Gil-Hernández, Sara; Ruelas-Perea, Ana; Villaverde-Rodríguez, Diego; Montes-Ochoa, José Roberto; Medrano-Guzmán, Rafael

Gastric cancer in Mexico is ranked third in both males and females. Most patients present clinically with advanced disease and treatment options are sparse. HER2 overexpression in gastric cancer is related to poor outcome. Immunohistochemical testing for HER2 is becoming the standard of care for guiding adjuvant treatment of gastric cancer with trastuzumab. To determine the frequency of HER2 overexpression in patients with gastric cancer in the Hospital de Oncología del Centro Médico Nacional, Siglo XXI and its association with other histopathological findings. Patients with gastric cancer who underwent surgery between March 12, 2006-August 31, 2011, were enrolled in this retrospective study. Diagnosis was confirmed by review of slides and immunohistochemistry with anti-HER2 antibody was performed. Scoring was done by Hoffman scoring system. Medical records were evaluated. Ninety-three patients were included in the study, with 43 (46.2%) male and 50 (53.7%) female patients. The median age was 64 years. HER2-positive tumours were identified in 6 patients (6.45%) and located most frequently in the proximal stomach. There was no difference in HER2 overexpression in relation to age, gender or histologic type. In our study, about 7% of patients with gastric cancer were HER2-positive on immunohistochemistry. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Pathobiology of Helicobacter pylori-induced Gastric Cancer

PubMed Central

Amieva, Manuel; Peek, Richard M.

2015-01-01

Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073

Hereditary diffuse gastric cancer: implications of genetic testing for screening and prophylactic surgery.

PubMed

Cisco, Robin M; Ford, James M; Norton, Jeffrey A

2008-10-01

Approximately 10% of patients with gastric cancer show familial clustering, and 3% show autosomal dominance and high penetrance. Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant, inherited cancer syndrome in which affected individuals develop diffuse-type gastric cancer at a young age. Inactivating mutations in the E-cadherin gene CDH1 have been identified in 30% to 50% of patients. CDH1 mutation carriers have an approximately 70% lifetime risk of developing DGC, and affected women carry an additional 20% to 40% risk of developing lobular breast cancer. Because endoscopic surveillance is ineffective in identifying early HDGC, gene-directed prophylactic total gastrectomy currently is offered for CDH1 mutation carriers. In series of asymptomatic individuals undergoing total gastrectomy for CDH1 mutations, the removed stomachs usually contain small foci of early DGC, making surgery not prophylactic but curative. The authors of this review recommend consideration of total gastrectomy in CDH1 mutation carriers at an age 5 years younger than the youngest family member who developed gastric cancer. Individuals who choose not to undergo prophylactic gastrectomy should be followed with biannual chromoendoscopy, and women with CDH1 mutations also should undergo regular surveillance with magnetic resonance imaging studies of the breast. Because of the emergence of gene-directed gastrectomy for HDGC, today, a previously lethal disease is detected by molecular techniques, allowing curative surgery at an early stage.

Clinical significance of nm23 gene expression in gastric cancer.

PubMed

Mönig, Stefan P; Nolden, Brit; Lübke, Thomas; Pohl, Alexandra; Grass, Guido; Schneider, Paul M; Dienes, Hans P; Hölscher, Arnulf H; Baldus, Stephan E

2007-01-01

The expression of the nm23 gene has been associated with the development of metastasis. Numerous studies have shown down-regulation of nm23 expression in metastatic breast and colon cancer. The expression of the putative metastasis-suppressor gene nm23 in gastric carcinoma is controversial. The aim of this study was the analysis of nm23 expression in a large series of gastric cancer patients. In a retrospective immunohistochemical study specimens obtained from 116 gastric cancer patients (mean age 64 years; range: 33-85) who had undergone gastrectomy with extended lymphadenectomy were analyzed. Nm23 expression in the tumor epithelium was studied by immunohistochemistry followed by a semi-quantitative (score 0-3) evaluation. Statistical analysis including Chi-square test, uni- and multivariate survival analyses were performed. The nm23 staining pattern was positive (score 2-3) in 100 (86.2%) specimens and negative (score 0-1) in 16 (13.8%) samples. Lymph node metastasis was found in 65% of the patients. No significant correlations could be determined between nm23 expression and other variables such as gender, age, tumor differentiation, WHO-, Laurén-, Goseki-, or Ming-classification. The intensity of nm23 staining in the tumor cells was not significantly correlated with depth of tumor infiltration (T-stage), lymph node metastasis (N-stage), distant metastasis (M-stage), UICC-stage, or prognosis. Our series did not show a correlation of nm23 expression in terms of lymph node and distant metastasis or prognosis in gastric cancer patients.

Quantitative assessment model for gastric cancer screening

PubMed Central

Chen, Kun; Yu, Wei-Ping; Song, Liang; Zhu, Yi-Min

2005-01-01

AIM: To set up a mathematic model for gastric cancer screening and to evaluate its function in mass screening for gastric cancer. METHODS: A case control study was carried on in 66 patients and 198 normal people, then the risk and protective factors of gastric cancer were determined, including heavy manual work, foods such as small yellow-fin tuna, dried small shrimps, squills, crabs, mothers suffering from gastric diseases, spouse alive, use of refrigerators and hot food, etc. According to some principles and methods of probability and fuzzy mathematics, a quantitative assessment model was established as follows: first, we selected some factors significant in statistics, and calculated weight coefficient for each one by two different methods; second, population space was divided into gastric cancer fuzzy subset and non gastric cancer fuzzy subset, then a mathematic model for each subset was established, we got a mathematic expression of attribute degree (AD). RESULTS: Based on the data of 63 patients and 693 normal people, AD of each subject was calculated. Considering the sensitivity and specificity, the thresholds of AD values calculated were configured with 0.20 and 0.17, respectively. According to these thresholds, the sensitivity and specificity of the quantitative model were about 69% and 63%. Moreover, statistical test showed that the identification outcomes of these two different calculation methods were identical (P>0.05). CONCLUSION: The validity of this method is satisfactory. It is convenient, feasible, economic and can be used to determine individual and population risks of gastric cancer. PMID:15655813

[Multivariate analysis of the association between consumption of fried food and gastric cancer and precancerous lesions].

PubMed

Guo, L W; Liu, S Z; Zhang, M; Chen, Q; Zhang, S K; Sun, X B

2018-02-06

Objective: To investigate the effect of fried food intake on the pathogenesis of gastric cancer and precancerous lesions. Methods: From 2005 to 2013, the residents aged 40-69 years from 11 counties/cities where cancer screening of upper gastrointestinal cancer were conducted in rural areas of Henan province as the subjects (82 367 cases). The information such as demography and lifestyle was collected. The residents were screened with endoscopic examination. The biopsy sampleswere diagnosed pathologically, according to pathological diagnosis criteria, the subjects with high risk were divided into the groups with different pathological degrees. The multivariate ordinal logistic regression analysis was used to analyze the relationship between the frequency of fried food intake and gastric cancer and precancerous lesions. Results: The study coverd 46 425 males and 35 942 females, with a age of (53.46±8.07)years. The study collected 6 707 cases of normal stomach, 2 325 cases of low grade intraepithelial neoplasia, 226 cases of high grade intraepithelial neoplasia and 331 cases of gastric cancer. Multivariate logistic regression analysis showed that, compared with those whoeat fried food less than one time per week, fried foods intake (<2 times/week: OR= 1.89, 95 %CI: 1.57-2.28; ≥ 2 times/week: OR= 1.91, 95 %CI: 1.66-2.20) were a risk factor for gastric cancer and precancerous lesions after adjustment for age, sex, marital status, educational level, body mass index (BMI), smoking and drinking status. Conclusion: The intake of fried food is a risk factor for gastric cancer and precancerous lesions. Therefore, reducing the intake of fried food can prevent the occurrence of gastric carcinoma and precancerous lesions.

Trends in oral cavity, pharyngeal, oesophageal and gastric cancer mortality rates in Spain, 1952-2006: an age-period-cohort analysis.

PubMed

Seoane-Mato, Daniel; Aragonés, Nuria; Ferreras, Eva; García-Pérez, Javier; Cervantes-Amat, Marta; Fernández-Navarro, Pablo; Pastor-Barriuso, Roberto; López-Abente, Gonzalo

2014-04-11

Although oral cavity, pharyngeal, oesophageal and gastric cancers share some risk factors, no comparative analysis of mortality rate trends in these illnesses has been undertaken in Spain. This study aimed to evaluate the independent effects of age, death period and birth cohort on the mortality rates of these tumours. Specific and age-adjusted mortality rates by tumour and sex were analysed. Age-period-cohort log-linear models were fitted separately for each tumour and sex, and segmented regression models were used to detect changes in period- and cohort-effect curvatures. Among men, the period-effect curvatures for oral cavity/pharyngeal and oesophageal cancers displayed a mortality trend that rose until 1995 and then declined. Among women, oral cavity/pharyngeal cancer mortality increased throughout the study period whereas oesophageal cancer mortality decreased after 1970. Stomach cancer mortality decreased in both sexes from 1965 onwards. Lastly, the cohort-effect curvature showed a certain degree of similarity for all three tumours in both sexes, which was greater among oral cavity, pharyngeal and oesophageal cancers, with a change point in evidence, after which risk of death increased in cohorts born from the 1910-1920s onwards and decreased among the 1950-1960 cohorts and successive generations. This latter feature was likewise observed for stomach cancer. While the similarities of the cohort effects in oral cavity/pharyngeal, oesophageal and gastric tumours support the implication of shared risk factors, the more marked changes in cohort-effect curvature for oral cavity/pharyngeal and oesophageal cancer could be due to the greater influence of some risk factors in their aetiology, such as smoking and alcohol consumption. The increase in oral cavity/pharyngeal cancer mortality in women deserves further study.

E-Cadherin and Gastric Cancer: Cause, Consequence, and Applications

PubMed Central

Liu, Xin

2014-01-01

E-cadherin (epithelial-cadherin), encoded by the CDH1 gene, is a transmembrane glycoprotein playing a crucial role in maintaining cell-cell adhesion. E-cadherin has been reported to be a tumor suppressor and to be down regulated in gastric cancer. Besides genetic mutations in CDH1 gene to induce hereditary diffuse gastric cancer (HDGC), epigenetic factors such as DNA hypermethylation also contribute to the reduction of E-cadherin in gastric carcinogenesis. In addition, expression of E-cadherin could be mediated by infectious agents such as H. pylori (Helicobacter pylori). As E-cadherin is vitally involved in signaling pathways modulating cell proliferation, survival, invasion, and migration, dysregulation of E-cadherin leads to dysfunction of gastric epithelial cells and contributes to gastric cancer development. Moreover, changes in its expression could reflect pathological conditions of gastric mucosa, making its role in gastric cancer complicated. In this review, we summarize the functions of E-cadherin and the signaling pathways it regulates. We aim to provide comprehensive perspectives in the molecular mechanism of E-cadherin and its involvement in gastric cancer initiation and progression. We also focus on its applications for early diagnosis, prognosis, and therapy in gastric cancer in order to open new avenues in this field. PMID:25184143

Molecular diagnostics in gastric cancer.

PubMed

Bornschein, Jan; Leja, Marcis; Kupcinskas, Juozas; Link, Alexander; Weaver, Jamie; Rugge, Massimo; Malfertheiner, Peter

2014-01-01

Despite recent advances in individualised targeted therapy, gastric cancer remains one of the most challenging diseases in gastrointestinal oncology. Modern imaging techniques using endoscopic filter devices and in vivo molecular imaging are designed to enable early detection of the cancer and surveillance of patients at risk. Molecular characterisation of the tumour itself as well as of the surrounding inflammatory environment is more sophisticated in the view of tailored therapies and individual prognostic assessment. The broad application of high throughput techniques for the description of genome wide patterns of structural (copy number aberrations, single nucleotide polymorphisms, methylation pattern) and functional (gene expression profiling, proteomics, miRNA) alterations in the cancer tissue lead not only to a better understanding of the tumour biology but also to a description of gastric cancer subtypes independent from classical stratification systems. Biostatistical means are required for the interpretation of the massive amount of data generated by these approaches. In this review we give an overview on the current knowledge of diagnostic methods for detection, description and understanding of gastric cancer disease.

The outcomes of esophageal and gastric cancer treatments in a retrospective study, single center experience.

PubMed

Alimoghaddam, Kamran; Jalali, Arash; Aliabadi, Leyla Sharifi; Ghaffari, Fatemeh; Maheri, Roghieh; Eini, Ezzat; Mashhadireza, Maryam; Mousavi, Seied Asadollah; Bahar, Babak; Jahani, Mohammad; Ghavamzadeh, Ardeshir

2014-01-01

Esophageal and gastric cancers are among the most common cancers in Iran. Usually survival of these cases is poor despite of treatment. Here we studied outcome of these cases in our center to have an estimation of general prognosis of patients. In this retrospective study, we reviewed the data of patient's files before treatment, including cancer stage at diagnosis, types of treatments and outcomes. We studied 368 patients treated between 1995 and 2011. The study included 368 patients (248 [67.4%] males and 120 [32.6%] females) with a median age of 58 (range: 23 - 94). Sixty nine patients (18.8%) had esophageal cancer with a median age of 58.5 years (range: 33 - 84), and 47.8% (33/69) of whom were male. Sixty five (17.7%) were reported to have gastro-esophageal junction (GEJ) with a median age of 62.0 (range: 32 - 94), among them 72.3% (47/65) of whom were male and finally Two hundred thirty four (63.6%) had gastric cancer with a median age of 57.0 (range: 23 - 82), which 71.8% (168/234) of whom were male. The Median follow-up was 10 months. The majority of patients were diagnosed at an advanced stage of disease. Stage III or IV was observed in 65.0% (39/60) of patients with esophageal cancer, 75.0% (33/44) with GEJ cancer and 65.4% (121/185) with gastric cancer. In this study, 58% of patients with esophageal cancer, 50.8% with GEJ and gastric cancers had unresectable disease or metastases at presentation. One-year EFS was 51.8% (95% CI: 39.8 - 67.3%), 32.8% (95% CI: 22.1 - 48.7%), and 56.7% (95% CI: 50.1 - 64.3%) in patients with esophageal, GEJ and gastric cancers, respectively (p = 0.002). The 1-year OS was 54.5% (95% CI: 42.6 - 69.8%), 39.5% (95 CI: 28.1 - 55.5%), and 68.2% (95% CI: 61.8 - 75.3%), respectively (p < 0.001). Cancers of the upper gastrointestinal (GI) tract contribute to the high mortality and morbidity rates because they are more likely to be diagnosed at late or advanced stages of disease. Cancer of the GEJ has a poor prognosis compared to

Diagnosis and Management of High Risk Group for Gastric Cancer

PubMed Central

Yoon, Hyuk; Kim, Nayoung

2015-01-01

Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval. PMID:25547086

Effects of legumain as a potential prognostic factor on gastric cancers.

PubMed

Li, Na; Liu, Qiaoling; Su, Qi; Wei, Chongyang; Lan, Bin; Wang, Jianyong; Bao, Guoqing; Yan, Fei; Yu, Ying; Peng, Baowei; Qiu, Ju; Yan, Xiangming; Zhang, Sheng; Guo, Fang

2013-01-01

Although legumain has been found to be a prognostic factor in both breast cancer and colorectal cancer, its effects on gastric cancer are unknown. In this study, we investigated effects of legumain on gastric cancer and the correlation between legumain expression and prognosis of gastric cancer patients. SGC7901 cells were transduced with legumain cDNA (SGC7901-hLeg) for overexpression of legumain or with legumain shRNA to knock down legumain. In vitro tumor migration was examined by wound healing assay. Furthermore, a tumorigenicity and metastasis mouse model was used to examine legumain function in vivo; asparaginyl endopeptidase inhibitor (AEPI, an inhibitor of legumain) was injected to the mice (i.p.) to evaluate its therapeutic effect. Tissue microarray analysis from 112 gastric cancer patients was performed to evaluate the association between legumain expression and the cumulative survival time. Legumain was highly expressed in gastric cancer patients and some gastric cancer cell lines. Legumain promoted gastric cell migration in vitro and promoted gastric tumor growth and metastasis in vivo, and these effects were reversed by knockdown of legumain with shRNA or treated with AEPI. In gastric cancer clinical samples, legumain expression in tumor was significantly higher than in non-tumor and was negatively associated with the cumulative survival rate. In conclusion, legumain was highly expressed in gastric adenocarcinoma; legumain promoted gastric cancer tumorigenesis and metastasis in vitro and in vivo. Legumain expression in tumor was a poor prognostic factor for gastric cancer patients, and legumain could be a potential target molecule for gastric cancer therapy in clinic.

Alterations of telomerase activity and terminal restriction fragment in gastric cancer and its premalignant lesions.

PubMed

Yang, S M; Fang, D C; Luo, Y H; Lu, R; Battle, P D; Liu, W W

2001-08-01

In order to explore the role of alterations of telomerase activity and terminal restriction fragment (TRF) length in the development and progression of gastric cancer. Telomerase activity was detected in 176 specimens of gastric mucosa obtained through an operation or endoscopical biopsy by using the telomeric repeat amplification protocol (TRAP) assay. Meanwhile, the mean length of TRF was measured with the use of a Southern blot in part of those samples. Telomerase activity was detected in 14 of 57 (24.6%) chronic atrophy gastritis patients, six of 18 (33.3%) intestinal metaplasia patients, three of eight (37.5%) dysplasia patients and 60 of 65 (92.3%) gastric cancer patients, respectively. Normal gastric mucosa revealed no telomerase activity. No association was found between telomerase activity and any clinicopathological parameters. The mean TRF length was decreased gradually with age in normal mucosa and in gastric cancer tissue. Regression analysis demonstrated that the reduction rate in these tissues was 41 +/- 12 base pairs/year. Among 35 gastric cancers, TRF length was shown to be shorter in 20 cases (57.1%), similar in 12 cases (34.3%) and elongated in three cases (7.6%), compared to the corresponding adjacent tissues. The mean TRF length tended to decrease as the mucosa underwent chronic atrophy gastritis, intestinal metaplasia, dysplasia and into gastric cancer. The mean TRF length in gastric cancer was not statistically correlated with clinicopathological parameters and telomerase activity. Our results suggest that telomerase is expressed during the early stage of gastric carcinogenesis, and that the clinical significance of TRF length appears to be limited in gastric cancer.

[Current standards in the treatment of gastric cancer].

PubMed

Hacker, Ulrich; Lordick, Florian

2015-08-01

Endoscopic resection is established in the treatment of early gastric cancer. More advanced gastric cancer requires gastrectomy and D2 lymphadenectomy. Perioperative chemotherapy improves overall survival in locally advanced gastric cancer representing a standard of care. Locally advanced adenocarcinomas of the esophago-gastric junction can alternatively be treated with concurrent radiochemotherapy. In metastatic disease, systemic chemotherapy improves survival, quality of life and symptom control. Trastuzumab plus chemotherapy should be used together with first-line chemotherapy in HER2 positive gastric cancer patients. Second- and third-line therapy is now well established. The anti-VEGFR2 antibody Ramucirumab improves survival in second line treatment both as a monotherapy and in combination with paclitaxel and represents a novel treatment option. © Georg Thieme Verlag KG Stuttgart · New York.

Coffee consumption and risk of gastric and pancreatic cancer--a prospective cohort study.

PubMed

Bidel, Siamak; Hu, Gang; Jousilahti, Pekka; Pukkala, Eero; Hakulinen, Timo; Tuomilehto, Jaakko

2013-04-01

Only few prospective studies have examined the association between coffee consumption and risk of gastric and pancreatic cancer. This study is designed to evaluate this relationship among Finns, whose coffee consumption is the highest in the world. A total of 60,041 Finnish men and women who were 26-74 years of age and without history of any cancer at baseline were included in the present analyses. Coffee consumption and other study parameters were determined at baseline using standardized measurements. Participants were prospectively followed up for onset of gastric and/or pancreatic cancer, emigration, death or until June 30, 2006. During a mean follow-up period of 18 years, 299 cases of gastric cancer and 235 cases of pancreatic cancer were found. There was a nonsignificant inverse association between coffee consumption and risk of gastric cancer among men but not in the women. The multivariate-adjusted hazard ratio of stomach and pancreatic cancer incidence for ≥ 10 cups of coffee per day compared with nondrinkers were 0.75 (95% CI, 0.40-1.41) (P for trend = 0.19) and 0.82 (95% CI, 0.38-1.76) (P for trend = 0.95) for the combined population of men and women, respectively. We did not find a significant association between coffee consumption and the risk of gastric and/or pancreatic cancers. Copyright © 2012 UICC.

Silencing NKD2 by promoter region hypermethylation promotes gastric cancer invasion and metastasis by up-regulating SOX18 in human gastric cancer.

PubMed

Jia, Yan; Cao, Baoping; Yang, Yunsheng; Linghu, Enqiang; Zhan, Qimin; Lu, Youyong; Yu, Yingyan; Herman, James G; Guo, Mingzhou

2015-10-20

Naked cuticle homolog2 (NKD2) is located in chromosome 5p15.3, which is frequently loss of heterozygosity in human colorectal and gastric cancers. In order to understand the mechanism of NKD2 in gastric cancer development, 6 gastric cancer cell lines and 196 cases of human primary gastric cancer samples were involved. Methylation specific PCR (MSP), gene expression array, flow cytometry, transwell assay and xenograft mice model were employed in this study. The expression of NKD1 and NKD2 was silenced by promoter region hypermethylation. NKD1 and NKD2 were methylated in 11.7% (23/196) and 53.1% (104/196) in human primary gastric cancer samples. NKD2 methylation is associated with cell differentiation, TNM stage and distant metastasis significantly (all P < 0.05), and the overall survival time is longer in NKD2 unmethylated group compared to NKD2 methylated group (P < 0.05). Restoration of NKD2 expression suppressed cell proliferation, colony formation, cell invasion and migration, induced G2/M phase arrest, and sensitized cancer cells to docetaxel. NKD2 inhibits SOX18 and MMP-2,7,9 expression and suppresses BGC823 cell xenograft growth. In conclusion, NKD2 methylation may serve as a poor prognostic and chemo-sensitive marker in human gastric cancer. NKD2 impedes gastric cancer metastasis by inhibiting SOX18.

Dietary factors and gastric cancer risk. A case-control study in Spain.

PubMed

Ramón, J M; Serra, L; Cerdó, C; Oromí, J

1993-03-01

Evidence supports that gastric cancer has an environmental etiology, of which diet appears to be the most important component. The authors examined the effect of diet on the risk of gastric cancer. A case-control study of dietary factors and gastric cancer was conducted between September 1986 and March 1989 in the Barcelona metropolitan area, Spain. One hundred seventeen cases with histologically confirmed diagnosis of gastric adenocarcinoma were matched by age, gender, and whether they possessed a telephone to 234 community controls. One hundred eighty-eight (80.3%) controls were selected by random-digit telephone dialing and 46 (19.7%) by neighborhood of residence. Information about frequency and amount of consumption of 89 food items in one year was gathered by using a questionnaire, and cases and controls were interviewed in their homes by trained interviewers. Unconditional logistic regression was used for the analysis. Gastric cancer risk rose with increasing intake of smoked and pickled foods (OR 3.67 for upper tertile) and salt (OR 2.11 for upper quartile). Intake of citrus fruits (OR 0.47 for upper tertile) and raw-green vegetables (OR 0.56 for upper quartile) appeared to be protective. Gastric cancer risk was not associated with intake of cereals, rice, total vegetables, and fruits as a whole. These data suggest that high intake of salt and smoked and pickled food may be associated with a high risk of gastric cancer, and this association could be due to intragastric formation of nitrosamines. The negative association with citric and green vegetables consumption to be associated with the inhibition of nitrosation process.

[Interleukin-10-1082 promoter polymorphism and the risk of gastric cancer].

PubMed

Yin, Yi-qiong; Liu, Chun-juan; Zhang, Ming-ming; Zhou, Yong

2012-05-01

To investigate the association between Interleukin-10 (IL-10) promoter polymorphism and the gastric cancer risk in Chinese Han patients. DNA was extracted from blood samples of gastric cancer patients (n = 75) and controls (n = 75). IL-10 -1082 promoter polymorphism in both patient and control group (three genotypes distribution: AA, AG and GG) was identified by PCR-RFLP and its relationship with gastric cancer risk, clinic and pathologic features was also analyzed. Patients with gastric cancer had a significantly lower frequency of AA (OR = 0.43, 95% CI = 0.20, 0.92; P = 0.03) than controls. Patients with proximal gastric cancer had a significantly higher frequency of GG (OR = 3.06, 95% CI = 1.12, 8.36; P = 0.03) than those with distant gastric cancer. Patients with advanced (stage II/IV) gastric cancer had a significantly higher frequency of AA (OR = 5.09, 95% CI = 1.05, 24.70; P = 0.04) than those with early (stage I /IV) gastric cancer. When stratified by the Lauren's classification, histological differentiation of gastric cancer, no statistically significant results was observed. This study suggests that the IL-1 1082 promoter polymorphism may be associated with gastric cancer in Chinese Han patients, and the difference in genotype distribution may be associated with the location and stage of gastric cancer.

Predictive value of CHFR and MLH1 methylation in human gastric cancer.

PubMed

Li, Yazhuo; Yang, Yunsheng; Lu, Youyong; Herman, James G; Brock, Malcolm V; Zhao, Po; Guo, Mingzhou

2015-04-01

Gastric carcinoma (GC) has one of the highest mortality rates of cancer diseases and has a high incidence rate in China. Palliative chemotherapy is the main treatment for advanced gastric cancer. It is necessary to compare the effectiveness and toxicities of different regimens. This study explores the possibility of methylation of DNA damage repair genes serving as a prognostic and chemo-sensitive marker in human gastric cancer. The methylation status of five DNA damage repair genes (CHFR, FANCF, MGMT, MLH1, and RASSF1A) was detected by nested methylation-specific PCR in 102 paraffin-embedded gastric cancer samples. Chi-square or Fisher's exact tests were used to evaluate the association of methylation status and clinic-pathological factors. The Kaplan-Meier method and Cox proportional hazards models were employed to analyze the association of methylation status and chemo-sensitivity. The results indicate that CHFR, MLH1, RASSF1A, MGMT, and FANCF were methylated in 34.3% (35/102), 21.6% (22/102), 12.7% (13/102), 9.8% (10/102), and 0% (0/102) of samples, respectively. No association was found between methylation of CHFR, MLH1, RASSF1A, MGMT, or FANCF with gender, age, tumor size, tumor differentiation, lymph node metastasis, and TNM stage. In docetaxel-treated gastric cancer patients, resistance to docetaxel was found in CHFR unmethylated patients by Cox proportional hazards model (HR 0.243, 95% CI, 0.069-0.859, p = 0.028), and overall survival is longer in the CHFR methylated group compared with the CHFR unmethylated group (log-rank, p = 0.036). In oxaliplatin-treated gastric cancer patients, resistance to oxaliplatin was found in MLH1 methylated patients (HR 2.988, 95% CI, 1.064-8.394, p = 0.038), and overall survival was longer in the MLH1 unmethylated group compared with the MLH1 methylated group (log-rank, p = 0.046). CHFR is frequently methylated in human gastric cancer, and CHFR methylation may serve as a docetaxel-sensitive marker. MLH1 methylation was

Overview of Current Concepts in Gastric Intestinal Metaplasia and Gastric Cancer.

PubMed

Jencks, David S; Adam, Jason D; Borum, Marie L; Koh, Joyce M; Stephen, Sindu; Doman, David B

2018-02-01

Gastric intestinal metaplasia is a precancerous change of the mucosa of the stomach with intestinal epithelium, and is associated with an increased risk of dysplasia and cancer. The pathogenesis to gastric cancer is proposed by the Correa hypothesis as the transition from normal gastric epithelium to invasive cancer via inflammation followed by intramucosal cancer and invasion. Multiple risk factors have been associated with the development of gastric intestinal metaplasia interplay, including Helicobacter pylori infection and associated genomics, host genetic factors, environmental milieu, rheumatologic disorders, diet, and intestinal microbiota. Globally, screening guidelines have been established in countries with high incidence. In the United States, no such guidelines have been developed due to lower, albeit increasing, incidence. The American Society for Gastrointestinal Endoscopy recommends a case-by-case patient assessment based upon epidemiology, genetics, and environmental risk factors. Studies have examined the use of a serologic biopsy to stratify risk based upon factors such as H pylori status and virulence factors, along with serologic markers of chronic inflammation including pepsinogen I, pepsinogen II, and gastrin. High-risk patients may then be advised to undergo endoscopic evaluation with mapping biopsies from the antrum (greater curvature, lesser curvature), incisura angularis, and corpus (greater curvature, lesser curvature). Surveillance guidelines have not been firmly established for patients with known gastric intestinal metaplasia, but include repeat endoscopy at intervals according to the histologic risk for malignant transformation.

New advances in targeted gastric cancer treatment.

PubMed

Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

2016-08-14

Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.

New advances in targeted gastric cancer treatment

PubMed Central

Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

2016-01-01

Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

Should every region use the same gastric cancer scanning and treatment approaches? let's reconsider: a northeastern turkey example.

PubMed

Fatih, Albayrak; Yasin, Ozturk; Hakan, Dursun; Yavuz, Albayrak

2016-10-04

The rate for upper gastrointestinal (UGI) cancers, and especially the rate for gastric cancer, varies from country to country and from region to region within country. In Turkey, the incidence of gastric cancer varies widely among regions due to the diverse cultures and accompanying food habits of the population. This study aimed to determine the endoscopic frequency of esophageal and gastric cancers and the usefulness of alarm symptoms in diagnosing gastric cancer in subjects undergoing endoscopy in northeastern Turkey. This retrospective study was based on hospital records, reviewing the records of patients who had underdone esophago-gastro-duodenal (EGD) video endoscopy at two general hospitals in Erzurum. From July 2010 to January 2013, 25,037 patients from Erzurum underwent EGD procedures under either intravenous sedation or local anesthesia. Classifications of UGI cancer, based on location of the tumor, were defined as esophageal, cardia, cardia and fundus or corpus or all of these, corpus, corpus and antrum, and antrum. Metastasis was studied in 659 patients diagnosed with cancer. Throughout the study, 1,007 biopsy samples were reported as malignant tumors (719 gastric, 276 esophageal, and 12 duodenal cancers). The study considered the gastric cancer population under age 46, which included 99 (13.8 %) patients. Among them, the distribution of UGI cancer by age was as follows: under age 26 years, 9 patients (0.9 %); age 26-35 years, 30 patients (3 %); and age 36-45 years, 60 patients (6 %). Overall, 298 patients (298/1007, 29.6 %) presented with localized disease, and 361 patients (35.9 %) had distant metastases at the time of diagnosis. We determined that UGI cancer patients are observed more frequently in northeastern Turkey than in western Turkey, Europe, and the USA. We believe that alarm symptoms and endoscopic scanning programs require new, region-specific criteria to diagnose UGI cancers in this region. For the patient groups with these

[Eleven Patients with Gastric Cancer Who Received Chemotherapy after Stent Placement for Gastric Outlet Obstruction].

PubMed

Endo, Shunji; Nakagawa, Tomo; Konishi, Ken; Ikenaga, Masakazu; Ohta, Katsuya; Nakashima, Shinsuke; Matsumoto, Kenichi; Nishikawa, Kazuhiro; Ohmori, Takeshi; Yamada, Terumasa

2017-01-01

Endoscopic placement of self-expandable metallic stents is reportedly effective for gastric outlet obstructions due to advanced gastric cancer, and is less invasive than gastrojejunostomy. For patients who have good performance status, we administer chemotherapy after stent placement, although the safety and feasibility of this chemotherapy have not yet been discussed in full. Between 2011 and 2015, 15 patients at our institution underwent endoscopic gastroduodenal stent placement for gastric outlet obstruction due to gastric cancer. Eleven of these patients were administered chemotherapy after stent placement. In our case series, we did not observe any specific adverse event caused by stent placement plus chemotherapy. Adverse events after chemotherapy included anemia of CTCAE Grade 3 in 7 patients. Stent-in-stent placement was needed in 2 patients. Neither stent migration nor perforation was observed. Therefore, chemotherapy after stent placement for gastric outlet obstruction due to gastric cancer was considered safe and feasible. Stent placement is useful not only as palliative care for patients with terminal-stage disease, but also as one of the multimodal therapeutic strategies for gastric cancer.

Molecular targeted therapy for the treatment of gastric cancer.

PubMed

Xu, Wenting; Yang, Zhen; Lu, Nonghua

2016-01-04

Despite the global decline in the incidence and mortality of gastric cancer, it remains one of the most common malignant tumors of the digestive system. Although surgical resection is the preferred treatment for gastric cancer, chemotherapy is the preferred treatment for recurrent and advanced gastric cancer patients who are not candidates for reoperation. The short overall survival and lack of a standard chemotherapy regimen make it important to identify novel treatment modalities for gastric cancer. Within the field of tumor biology, molecular targeted therapy has attracted substantial attention to improve the specificity of anti-cancer efficacy and significantly reduce non-selective resistance and toxicity. Multiple clinical studies have confirmed that molecular targeted therapy acts on various mechanisms of gastric cancer, such as the regulation of epidermal growth factor, angiogenesis, immuno-checkpoint blockade, the cell cycle, cell apoptosis, key enzymes, c-Met, mTOR signaling and insulin-like growth factor receptors, to exert a stronger anti-tumor effect. An in-depth understanding of the mechanisms that underlie molecular targeted therapies will provide new insights into gastric cancer treatment.

Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers.

PubMed

Wu, Hua-Hsi; Lin, Wen-chang; Tsai, Kuo-Wang

2014-01-23

Carcinoma of the stomach is one of the most prevalent cancer types in the world. Although the incidence of gastric cancer is declining, the outcomes of gastric cancer patients remain dismal because of the lack of effective biomarkers to detect early gastric cancer. Modern biomedical research has explored many potential gastric cancer biomarker genes by utilising serum protein antigens, oncogenic genes or gene families through improving molecular biological technologies, such as microarray, RNA-Seq and the like. Recently, the small noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the oncogenesis pathways and to serve as useful clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis, including gastric cancer. By translational suppression of target genes, miRNAs play a significant role in the gastric cancer cell physiology and tumour progression. There are potential implications of previously discovered gastric cancer molecular biomarkers and their expression modulations by respective miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour-suppressing functions in human cancers. With the surprising stability of miRNAs in tissues, serum or other body fluids, miRNAs have emerged as a new type of cancer biomarker with immeasurable clinical potential.

Impact of Age on the Prognosis of Operable Gastric Cancer Patients: An Analysis Based on SEER Database.

PubMed

Chen, Jie; Chen, Jinggui; Xu, Yu; Long, Ziwen; Zhou, Ye; Zhu, Huiyan; Wang, Yanong; Shi, Yingqiang

2016-06-01

To investigate the impact of age on the clinicopathological features and survival of patients with gastric cancer (GC), and hope to better define age-specific patterns of GC and possible associated risk factors.Using the surveillance, epidemiology, and end results (SEER) database to search the patients who diagnosed GC between 2007 and 2011 with a known age. The overall and 5-year gastric cancer specific survival (CSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors.A total of 7762 GC patients treated with surgery during the 4-year study period were included in the final study cohort. We divided into five subgroups according to the different age ranges. The overall 5-year cause-specific survival (CSS) was 60.3% in Group 1 (below 45 years), 60.3% in the Group 2 (45-55 years), 61.2% in Group 3 (56-65 years), 59.2% in Group 4 (66-75 years), and 59.2% in Group 5 (older than 76 years). Kaplan-Meier plots showed that patients older than 76 years had the worst 5-year CSS of 56.0% rate in all the subgroups. Age, tumor size, primary site, histological type, and Tumor Node Metastasis stage were identified as significant risk factors for poor survival on univariate analysis (all P < 0.001, log-rank test). Additionally, as the age increased, the risk of death for GC demonstrated a significant increase.In conclusion, our analysis of the SEER database revealed that the prognosis of GC varies with age. Patients at age 56 to 65 group have more favorable clinicopathologic characteristics and better CSS than other groups.

Factors affecting mortality in elderly patients who underwent surgery for gastric cancer.

PubMed

Kayılıoglu, Selami Ilgaz; Göktug, Ufuk Utku; Dinc, Tolga; Sozen, Isa; Yavuz, Zeynep; Coskun, Faruk

2018-03-05

The aim of this study was to determine factors affecting overall mortality in patients over 60 years of age who underwent surgery for gastric cancer in our clinic. Data on histopathological diagnosis (tumor size, lymph node status, and number), pathological stage, serum albumin level, tumor markers, complete blood count, and demographic information of 109 patients over 60 years of age who had surgery for gastric cancer between January 2011 and July 2016 were obtained retrospectively from the patient files. In addition, the survival status of all patients were examined and recorded. Metastatic lymph node ratio (MLR), red cell distribution width platelet ratio (RPR), neutrophil-lymphocyte ratio (NLR), plateletlymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated. On univariate analysis of independent parameters, pathological LN number (p = 0.001), MLR (p <0.001), T3 (p = 0.001) or T4 (p = 0,006) tumor stage according to TNM system, the presence of metastasis (p = 0.063), and male gender (p = 0.066) were found to affect overall mortality (OM). On multivariable Cox regression analysis of these results, MLR (p = 0.005) and T stage (p = 0.006) was determined to be a statistically significant and independent prognostic value. In patients over 60 years of age who underwent surgery for gastric cancer, the factors affecting mortality were determined to be the presence of metastases, number of pathological lymph nodes, and male gender. Metastatic lymph node ratio and T1&T2 stage were determined to be independent prognostic factors. Elderly, Gastric cancer, Mortality, Prognostic factor.

T staging of gastric cancer: role of multi-detector row CT.

PubMed

Kumano, Seishi; Murakami, Takamichi; Kim, Tonsok; Hori, Masatoshi; Iannaccone, Riccardo; Nakata, Saki; Onishi, Hiromitsu; Osuga, Keigo; Tomoda, Kaname; Catalano, Carlo; Nakamura, Hironobu

2005-12-01

To evaluate retrospectively the accuracy of multi-detector row computed tomography (CT) in the assessment of serosal invasion in patients with gastric cancer. The Ethics Committee does not require approval or informed consent for retrospective studies. Forty-one consecutive patients (24 men, 17 women; mean age, 68 years) with gastric cancer were included in this study. All patients were given 600 mL of tap water to drink and were positioned prone or supine on the scanning table. The detector row configuration included four detector rows, a section thickness of 1.25 mm, a pitch of 6, and a reconstruction interval of 0.63 mm. Transverse and multiplanar reconstruction images were simultaneously evaluated by two independent observers to assess the depth of tumor invasion in the gastric wall (ie, T stage). T staging at multi-detector row CT was compared with T staging at histologic evaluation (reference standard), which was performed by means of surgical or histologic examination of the resected specimen. We also calculated the sensitivity, specificity, and accuracy of multi-detector row CT for each observer in the assessment of serosal invasion. Analysis of interobserver agreement showed substantial or almost perfect agreement (nonweighted kappa value of 0.78 and weighted kappa value of 0.85). Correct assessment of gastric wall invasion was 80% and 85% for observers 1 and 2, respectively. The sensitivity, specificity, and accuracy of multi-detector row CT in the assessment of serosal invasion were 90%, 95%, and 93%, respectively, for observer 1 and 80%, 97%, and 93%, respectively, for observer 2. Overstaging occurred in six patients, and understaging occurred in five patients. All understaged tumors were scirrhous subtype gastric cancer. Multi-detector row CT scanning of patients with gastric cancer gave 93% accuracy in the assessment of serosal invasion in patients with gastric cancer. RSNA, 2005

Risk of Gastric Cancer Among Patients With Intestinal Metaplasia of the Stomach in a US Integrated Health Care System.

PubMed

Reddy, Kavya M; Chang, Jonathan I; Shi, Jiaxiao M; Wu, Bechien U

2016-10-01

Gastric intestinal metaplasia (GIM) is a common finding from routine endoscopies. Although GIM is an early step in gastric carcinogenesis, there is controversy regarding routine surveillance of patients with GIM in regions with a low prevalence of gastric cancer. We aimed to determine the incidence of gastric cancer among patients with GIM and risk factors for gastric cancer. We performed a retrospective cohort study of patients from the Kaiser Permanente Southern California region diagnosed with GIM from 2000 through 2011. GIM was identified by a keyword search of pathology reports; gastric cancer cases were identified by cross-reference with an internal cancer registry. The incidence of gastric cancer in patients with GIM (n = 923; median age at diagnosis, 68 y) was compared with that of an age- and sex-matched reference population (controls). Risk factors such as ethnicity, smoking status, history of Helicobacter pylori infection, and family history of gastric cancer were evaluated by individual Cox proportional hazards regression. We then performed a second case-cohort study to evaluate the risk of gastric cancer based on the location and extent of GIM. The median duration of follow-up evaluation was 4.6 years (interquartile range, 3.0-6.7 y). We identified 25 patients with GIM who developed gastric cancers. Seventeen cases of cancer were diagnosed at the same time as the diagnosis of GIM. Eight cases of cancer were identified within a median time period of 4.6 years after a diagnosis of GIM (interquartile range, 2-5.7 y). The overall incidence rate for the cohort was 1.72 (95% confidence interval, 0.74-3.39). Among the risk factors evaluated, only family history (hazard ratio, 3.8; 95% confidence interval, 1.5-9.7; P = .012) and extent of GIM (odds ratio, 9.4; 95% confidence interval, 1.8-50.4) increased the risk for gastric cancer. The incidence rate for gastric cancer in patients with a positive family history was 8.12 (95% confidence interval, 1

Incidence and survival for gastric and esophageal cancer diagnosed in British Columbia, 1990 to 1999

PubMed Central

Bashash, Morteza; Shah, Amil; Hislop, Greg; Brooks-Wilson, Angela; Le, Nhu; Bajdik, Chris

2008-01-01

BACKGROUND: Geographical variation and temporal trends in the incidence of esophageal and gastric cancers vary according to both tumour morphology and organ subsite. Both diseases are among the deadliest forms of cancer. The incidence and survival rates for gastric and esophageal carcinoma in British Columbia (BC) between 1990 and 1999 are described. METHODS: Incidence data for the period 1990 to 1999 were obtained from the BC Cancer Registry. Age-adjusted incidence and survival rates were computed by anatomical subsite, histological type and sex. All rates were standardized to the 1996 Canadian population. The estimated annual percentage change (EAPC) was used to measure incidence changes over time. Kaplan-Meier curves were used to show survival rates, and log-rank tests were used to test for differences in the curves among various groups. RESULTS: Between 1990 and 1999, 1741 esophageal cancer cases and 3431 gastric cancer cases were registered in BC. There was an increase in the incidence of adenocarcinoma of the esophagus over time (EAPC=9.6%) among men, and of gastric cardia cancer among both women (EAPC=9.2%) and men (EAPC=3.8%). Patients with proximal gastric (cardia) cancer had significantly better survival rates than patients with cancer in the lower one-third of the esophagus. Among gastric cancers, patients with distal tumours had a significantly better survival rate than patients with proximal tumours. DISCUSSION: The incidences of proximal gastric cancer and esophageal adenocarcinoma are increasing, and their survival patterns are different. Examining these cancers together may elucidate new etiological and prognostic factors. PMID:18299732

Stomach (Gastric) Cancer Screening (PDQ®)—Patient Version

Cancer.gov

There is no standard or routine screening test for stomach (gastric) cancer. Stomach (gastric) cancer is not common in the U.S. Learn about tests that have been studied to detect or screen for stomach cancer in this expert-reviewed summary.

Roles of long non-coding RNAs in gastric cancer metastasis

PubMed Central

Yang, Zi-Guo; Gao, Ling; Guo, Xiao-Bo; Shi, Yu-Long

2015-01-01

Gastric cancer is the second leading cause of cancer-related deaths. Metastasis, which is an important element of gastric cancer, leads to a high mortality rate and to a poor prognosis. Gastric cancer metastasis has a complex progression that involves multiple biological processes. The comprehensive mechanisms of metastasis remain unclear, though traditional regulation modulates the molecular functions associated with metastasis. Long non-coding RNAs (lncRNAs) have a role in different gene regulatory pathways by epigenetic modification and by transcriptional and post-transcription regulation. lncRNAs participate in various diseases, including Alzheimer’s disease, cardiovascular disease, and cancer. The altered expressions of certain lncRNAs are linked to gastric cancer metastasis and invasion, as with tumor suppressor genes or oncogenes. Studies have partly elucidated the roles of lncRNAs as biomarkers and in therapies, as well as their gene regulatory mechanisms. However, comprehensive knowledge regarding the functional mechanisms of gene regulation in metastatic gastric cancer remains scarce. To provide a theoretical basis for therapeutic intervention in metastatic gastric cancer, we reviewed the functions of lncRNAs and their regulatory roles in gastric cancer metastasis. PMID:25954095

Ethnicity in relation to incidence of oesophageal and gastric cancer in England.

PubMed

Coupland, V H; Lagergren, J; Konfortion, J; Allum, W; Mendall, M A; Hardwick, R H; Linklater, K M; Møller, H; Jack, R H

2012-11-20

This study investigated the variation in incidence of all, and six subgroups of, oesophageal and gastric cancer between ethnic groups. Data on all oesophageal and gastric cancer patients diagnosed between 2001 and 2007 in England were analysed. Self-assigned ethnicity from the Hospital Episode Statistics dataset was used. Male and female age-standardised incidence rate ratios (IRRs) were calculated for each ethnic group, using White groups as the references. Ethnicity information was available for 83% of patients (76 130/92 205). White men had a higher incidence of oesophageal cancer, with IRR for the other ethnic groups ranging from 0.17 95% confidence interval (CI) (0.15-0.20) (Pakistani men) to 0.58 95% CI (0.50-0.67) (Black Caribbean men). Compared with White women, Bangladeshi women (IRR 2.02 (1.24-3.29)) had a higher incidence of oesophageal cancer. For gastric cancer, Black Caribbean men (1.39 (1.22-1.60)) and women (1.57 (1.28-1.92)) had a higher incidence compared with their White counterparts. In the subgroup analysis, White men had a higher incidence of lower oesophageal and gastric cardia cancer compared with the other ethnic groups studied. Bangladeshi women (3.10 (1.60-6.00)) had a higher incidence of upper and middle oesophageal cancer compared with White women. Substantial ethnic differences in the incidence of oesophageal and gastric cancer were found. Further research into differences in exposures to risk factors between ethnic groups could elucidate why the observed variation in incidence exists.

A Rising Trend in the Incidence of Advanced Gastric Cancer in Young Hispanic Men

PubMed Central

Merchant, Shaila J.; Kim, Joseph; Choi, Audrey H.; Sun, Virginia; Chao, Joseph; Nelson, Rebecca

2017-01-01

BACKGROUND Although the incidence of gastric cancer has been decreasing, recent reports suggest an increased rate in select populations. We sought to evaluate trends in gastric cancer incidence to identify high risk populations. METHODS Gastric cancer incidence rates from 1992 to 2011 were computed using the Surveillance, Epidemiology and End Results (SEER) registry. We evaluated trends in incidence rates by calculating annual percent change (APC) across 3 age groups (20–49, 50–64, ≥65) and 4 racial/ethnic groups (Hispanics, non-Hispanic Whites, Blacks, and Asian/Pacific Islanders). RESULTS We identified 41,428 patients with gastric cancer. For the entire cohort over the study period, the APC was decreased. When patients were grouped according to sex, APC was flat or decreased in women regardless of age or race/ethnicity. APC was also flat or decreased for all men except young Hispanic males (20–49 years), who had an increased APC of nearly 1.6% per year (1.55%, 95% CI:0.26 to 2.86%). Furthermore, young Hispanic males were the only group to have increased incidence of Stage 4 disease (APC 4.34%, 95% CI:2.76 to 5.94%) and poorly differentiated tumors (APC 2.08%, 95% CI:0.48 to 3.70%). CONCLUSIONS The APC of young Hispanic male gastric cancer places it among the top cancers with rising incidence in the United States. This is concomitant with increased incidence of advanced disease at presentation. This major public health concern warrants additional research to determine the etiology of the increasing incidence in this group. PMID:26924751

Trends in oral cavity, pharyngeal, oesophageal and gastric cancer mortality rates in Spain, 1952–2006: an age-period-cohort analysis

PubMed Central

2014-01-01

Background Although oral cavity, pharyngeal, oesophageal and gastric cancers share some risk factors, no comparative analysis of mortality rate trends in these illnesses has been undertaken in Spain. This study aimed to evaluate the independent effects of age, death period and birth cohort on the mortality rates of these tumours. Methods Specific and age-adjusted mortality rates by tumour and sex were analysed. Age-period-cohort log-linear models were fitted separately for each tumour and sex, and segmented regression models were used to detect changes in period- and cohort-effect curvatures. Results Among men, the period-effect curvatures for oral cavity/pharyngeal and oesophageal cancers displayed a mortality trend that rose until 1995 and then declined. Among women, oral cavity/pharyngeal cancer mortality increased throughout the study period whereas oesophageal cancer mortality decreased after 1970. Stomach cancer mortality decreased in both sexes from 1965 onwards. Lastly, the cohort-effect curvature showed a certain degree of similarity for all three tumours in both sexes, which was greater among oral cavity, pharyngeal and oesophageal cancers, with a change point in evidence, after which risk of death increased in cohorts born from the 1910-1920s onwards and decreased among the 1950–1960 cohorts and successive generations. This latter feature was likewise observed for stomach cancer. Conclusions While the similarities of the cohort effects in oral cavity/pharyngeal, oesophageal and gastric tumours support the implication of shared risk factors, the more marked changes in cohort-effect curvature for oral cavity/pharyngeal and oesophageal cancer could be due to the greater influence of some risk factors in their aetiology, such as smoking and alcohol consumption. The increase in oral cavity/pharyngeal cancer mortality in women deserves further study. PMID:24725381

Gastric washing by distilled water can reduce free gastric cancer cells exfoliated into the stomach lumen.

PubMed

Ohki, Atsuko; Abe, Nobutsugu; Yoshimoto, Eri; Hashimoto, Yoshikazu; Takeuchi, Hirohisa; Nagao, Gen; Masaki, Tadahiko; Mori, Toshiyuki; Ohkura, Yasuo; Sugiyama, Masanori

2018-04-25

Intragastric free cancer cells in patients with gastric cancer have rarely been studied. The purpose of this study was to investigate the detection rate of intragastric free cancer cells in gastric washes using two types of solutions during endoscopic examination. We further clarified risk factors affecting the presence of exfoliated free cancer cells. A total of 175 patients with gastric cancer were enrolled. Lactated Ringer's solution (N = 89) or distilled water (DW; N = 86) via endoscopic working channel was sprayed onto the tumor surface, and the resultant fluid was collected for cytological examination. We compared the cancer-cell positivity rate between the two (Ringer and DW) groups. We also tested the correlation between cancer-cell positivity and clinicopathological factors in the Ringer group to identify risk factors for the presence of exfoliated cancer cells. The cancer-cell positivity rate was significantly higher in the Ringer group than that in the DW group (58 vs 6%). Cytomorphology in the Ringer group was well maintained, but not in the DW group. The larger tumor size (≥ 20 mm) and positive lymphatic involvement were significant risk factors of exfoliated free cancer cells. Cancer cells can be highly exfoliated from the tumor surface into the gastric lumen by endoscopic irrigation in large gastric cancer with lymphatic involvement. Gastric washing by DW can lead to cytoclasis of free cancer cells; therefore, it may minimize the possibility of cancer-cell seeding in procedures carrying potential risks of tumor-cell seeding upon transluminal communication, such as endoscopic full-thickness resection and laparoscopy-endoscopy cooperative surgery.

Short-term and long-term risk factors in gastric cancer

PubMed Central

Verlato, Giuseppe; Marrelli, Daniele; Accordini, Simone; Bencivenga, Maria; Di Leo, Alberto; Marchet, Alberto; Petrioli, Roberto; Zoppini, Giacomo; Muggeo, Michele; Roviello, Franco; de Manzoni, Giovanni

2015-01-01

While in chronic diseases, such as diabetes, mortality rates slowly increases with age, in oncological series mortality usually changes dramatically during the follow-up, often in an unpredictable pattern. For instance, in gastric cancer mortality peaks in the first two years of follow-up and declines thereafter. Also several risk factors, such as TNM stage, largely affect mortality in the first years after surgery, while afterward their effect tends to fade. Temporal trends in mortality were compared between a gastric cancer series and a cohort of type 2 diabetic patients. For this purpose, 937 patients, undergoing curative gastrectomy with D1/D2/D3 lymphadenectomy for gastric cancer in three GIRCG (Gruppo Italiano Ricerca Cancro Gastrico = Italian Research Group for Gastric Cancer) centers, were compared with 7148 type 2 diabetic patients from the Verona Diabetes Study. In the early/advanced gastric cancer series, mortality from recurrence peaked to 200 deaths per 1000 person-years 1 year after gastrectomy and then declined, becoming lower than 40 deaths per 1000 person-years after 5 years and lower than 20 deaths after 8 years. Mortality peak occurred earlier in more advanced T and N tiers. At variance, in the Verona diabetic cohort overall mortality slowly increased during a 10-year follow-up, with ageing of the type 2 diabetic patients. Seasonal oscillations were also recorded, mortality being higher during winter than during summer. Also the most important prognostic factors presented a different temporal pattern in the two diseases: while the prognostic significance of T and N stage markedly decrease over time, differences in survival among patients treated with diet, oral hypoglycemic drugs or insulin were consistent throughout the follow-up. Time variations in prognostic significance of main risk factors, their impact on survival analysis and possible solutions were evaluated in another GIRCG series of 568 patients with advanced gastric cancer, undergoing

Short-term and long-term risk factors in gastric cancer.

PubMed

Verlato, Giuseppe; Marrelli, Daniele; Accordini, Simone; Bencivenga, Maria; Di Leo, Alberto; Marchet, Alberto; Petrioli, Roberto; Zoppini, Giacomo; Muggeo, Michele; Roviello, Franco; de Manzoni, Giovanni

2015-06-07

While in chronic diseases, such as diabetes, mortality rates slowly increases with age, in oncological series mortality usually changes dramatically during the follow-up, often in an unpredictable pattern. For instance, in gastric cancer mortality peaks in the first two years of follow-up and declines thereafter. Also several risk factors, such as TNM stage, largely affect mortality in the first years after surgery, while afterward their effect tends to fade. Temporal trends in mortality were compared between a gastric cancer series and a cohort of type 2 diabetic patients. For this purpose, 937 patients, undergoing curative gastrectomy with D1/D2/D3 lymphadenectomy for gastric cancer in three GIRCG (Gruppo Italiano Ricerca Cancro Gastrico = Italian Research Group for Gastric Cancer) centers, were compared with 7148 type 2 diabetic patients from the Verona Diabetes Study. In the early/advanced gastric cancer series, mortality from recurrence peaked to 200 deaths per 1000 person-years 1 year after gastrectomy and then declined, becoming lower than 40 deaths per 1000 person-years after 5 years and lower than 20 deaths after 8 years. Mortality peak occurred earlier in more advanced T and N tiers. At variance, in the Verona diabetic cohort overall mortality slowly increased during a 10-year follow-up, with ageing of the type 2 diabetic patients. Seasonal oscillations were also recorded, mortality being higher during winter than during summer. Also the most important prognostic factors presented a different temporal pattern in the two diseases: while the prognostic significance of T and N stage markedly decrease over time, differences in survival among patients treated with diet, oral hypoglycemic drugs or insulin were consistent throughout the follow-up. Time variations in prognostic significance of main risk factors, their impact on survival analysis and possible solutions were evaluated in another GIRCG series of 568 patients with advanced gastric cancer, undergoing

Overview of Current Concepts in Gastric Intestinal Metaplasia and Gastric Cancer

PubMed Central

Adam, Jason D.; Borum, Marie L.; Koh, Joyce M.; Stephen, Sindu

2018-01-01

Gastric intestinal metaplasia is a precancerous change of the mucosa of the stomach with intestinal epithelium, and is associated with an increased risk of dysplasia and cancer. The pathogenesis to gastric cancer is proposed by the Correa hypothesis as the transition from normal gastric epithelium to invasive cancer via inflammation followed by intramucosal cancer and invasion. Multiple risk factors have been associated with the development of gastric intestinal metaplasia interplay, including Helicobacter pylori infection and associated genomics, host genetic factors, environmental milieu, rheumatologic disorders, diet, and intestinal microbiota. Globally, screening guidelines have been established in countries with high incidence. In the United States, no such guidelines have been developed due to lower, albeit increasing, incidence. The American Society for Gastrointestinal Endoscopy recommends a case-by-case patient assessment based upon epidemiology, genetics, and environmental risk factors. Studies have examined the use of a serologic biopsy to stratify risk based upon factors such as H pylori status and virulence factors, along with serologic markers of chronic inflammation including pepsinogen I, pepsinogen II, and gastrin. High-risk patients may then be advised to undergo endoscopic evaluation with mapping biopsies from the antrum (greater curvature, lesser curvature), incisura angularis, and corpus (greater curvature, lesser curvature). Surveillance guidelines have not been firmly established for patients with known gastric intestinal metaplasia, but include repeat endoscopy at intervals according to the histologic risk for malignant transformation. PMID:29606921

Effect of age on rates of palliative surgery and chemotherapy use in patients with locally advanced or metastatic gastric cancer.

PubMed

Nelen, S D; van Putten, M; Lemmens, V E P P; Bosscha, K; de Wilt, J H W; Verhoeven, R H A

2017-12-01

This study assessed trends in the treatment and survival of palliatively treated patients with gastric cancer, with a focus on age-related differences. For this retrospective, population-based, nationwide cohort study, all patients diagnosed between 1989 and 2013 with non-cardia gastric cancer with metastasized disease or invasion into adjacent structures were selected from the Netherlands Cancer Registry. Trends in treatment and 2-year overall survival were analysed and compared between younger (age less than 70 years) and older (aged 70 years or more) patients. Analyses were done for five consecutive periods of 5 years, from 1989-1993 to 2009-2013. Multivariable logistic regression analysis was used to examine the probability of undergoing surgery. Multivariable Cox regression analysis was used to identify independent risk factors for death. Palliative resection rates decreased significantly in both younger and older patients, from 24·5 and 26·2 per cent to 3·0 and 5·0 per cent respectively. Compared with patients who received chemotherapy alone, both younger (21·6 versus 6·3 per cent respectively; P < 0·001) and older (14·7 versus 4·6 per cent; P < 0·001) patients who underwent surgery had better 2-year overall survival rates. Multivariable analysis demonstrated that younger and older patients who received chemotherapy alone had worse overall survival than patients who had surgery only (younger: hazard ratio (HR) 1·22, 95 per cent c.i. 1·12 to 1·33; older: HR 1·12, 1·01 to 1·24). After 2003 there was no association between period of diagnosis and overall survival in younger or older patients. Despite changes in the use of resection and chemotherapy as palliative treatment, overall survival rates of patients with advanced and metastatic gastric cancer did not improve. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Clinicopathologic and prognostic characteristics of alpha-fetoprotein–producing gastric cancer

PubMed Central

Dong, Xuqiang; Wang, Yao; Zhang, Weiming; Shen, Lizong; Zhang, Zhihong

2017-01-01

Alpha-fetoprotein–producing gastric cancer (AFPGC) accounts for 1.5%–7.1% of all gastric cancer cases. Compared with other types of gastric cancer, AFPGC is more aggressive and prone to liver and lymph node (LN) metastasis, with extremely poor prognosis. To improve understanding of AFPGC we reviewed a consecutive series of 82 AFPGC patients and investigated the prognostic factors. The incidence of AFPGC among our gastric cancer patients was 1.95%, and 29.27% of AFPGCs were diagnosed with metastasis at the time of presentation, mainly liver metastasis. The serum AFP level of patients with AFPGC was significantly associated with tumor differentiation. Histologically, these AFPGC patients were composed of 34.55% hapatiod type, 58.18% fetal gastrointestinal type, 9.09% yolk sac tumor-like type, and 14.55% mixed type. Patient gender, tumor differentiation, Lauren classification, and number of metastatic lymph nodes showed significant differences among these four subtypes. The overall survival time was 42.02 months and the 3-year cumulative survival rate was 53.13%. Age, American Joint Committee on Cancer (AJCC) TNM staging classification (TNM stage), serum AFP level, and surgery were prognostic factors for overall survival; however, TNM stage was the only independent risk factor for prognosis of AFPGC. In short, AFPGC is a rare, unique, and heterogeneous entity, and its proper identification and treatment remain a challenge. More attention should be paid to AFPGC to improve patient care and the dismal prognosis. PMID:28423604

Clinicopathologic and prognostic characteristics of alpha-fetoprotein-producing gastric cancer.

PubMed

He, Ruji; Yang, Qinyi; Dong, Xuqiang; Wang, Yao; Zhang, Weiming; Shen, Lizong; Zhang, Zhihong

2017-04-04

Alpha-fetoprotein-producing gastric cancer (AFPGC) accounts for 1.5%-7.1% of all gastric cancer cases. Compared with other types of gastric cancer, AFPGC is more aggressive and prone to liver and lymph node (LN) metastasis, with extremely poor prognosis. To improve understanding of AFPGC we reviewed a consecutive series of 82 AFPGC patients and investigated the prognostic factors. The incidence of AFPGC among our gastric cancer patients was 1.95%, and 29.27% of AFPGCs were diagnosed with metastasis at the time of presentation, mainly liver metastasis. The serum AFP level of patients with AFPGC was significantly associated with tumor differentiation. Histologically, these AFPGC patients were composed of 34.55% hapatiod type, 58.18% fetal gastrointestinal type, 9.09% yolk sac tumor-like type, and 14.55% mixed type. Patient gender, tumor differentiation, Lauren classification, and number of metastatic lymph nodes showed significant differences among these four subtypes. The overall survival time was 42.02 months and the 3-year cumulative survival rate was 53.13%. Age, American Joint Committee on Cancer (AJCC) TNM staging classification (TNM stage), serum AFP level, and surgery were prognostic factors for overall survival; however, TNM stage was the only independent risk factor for prognosis of AFPGC. In short, AFPGC is a rare, unique, and heterogeneous entity, and its proper identification and treatment remain a challenge. More attention should be paid to AFPGC to improve patient care and the dismal prognosis.

Development of gastric cancer associated with Helicobacter pylori infection.

PubMed

Sugiyama, Toshiro

2004-09-01

Helicobacter pylori infection is associated with histological gastritis, gastric atrophy, gastric cancer and mucosa-associated lymphoid tissue lymphoma in the stomach. However, gastric cancer only develops in a minority of infected individuals. Such clinical diversity is caused by variations in the interactions between H. pylori pathogenicity, host susceptibility, and environmental factors. Based on evidence from three prospective epidemiological studies, the International Agency for Research on Cancer and the World Health Organization (IARC/WHO) concluded in 1994 that H. pylori has a causal linkage to gastric carcinogenesis and is a definite carcinogen in humans. Two large-scale, prospective, epidemiological studies have recently been reported in Japan and have confirmed that H. pylori infection constitutes a high risk factor for the development of gastric cancer, at least in males. In order to obtain evidence that eradication of H. pylori leads to a reduction in the occurrence of gastric cancer, reversibility of precancerous lesions, gastric atrophy or intestinal metaplasia should be proven after eradication treatment. A biopsy specimen from the lesser curvature of the corpus is the most sensitive for evaluating the regression of gastric atrophy on histology, and the evaluation needs be conducted at least 13 months after treatment. In a Mongolian gerbil model with or without low-dose chemical carcinogens, it has been demonstrated that H. pylori can lead to the development of gastric cancer. Experimental studies have elucidated that virulence factors of H. pylori interact with gastric epithelial cell signaling related to carcinogenesis. The cag pathogenicity island (cagPAI) is a major virulence gene cluster; it encodes the type IV secretion machinery system forming a cylinder-like structure. The CagA protein is translocated into target cells via this secretion system and induces a hummingbird phenotype, a growth factor-like effect. The other gene products are

Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathway.

PubMed

Gao, Yunhe; Cai, Aizhen; Xi, Hongqing; Li, Jiyang; Xu, Wei; Zhang, Yanmei; Zhang, Kecheng; Cui, Jianxin; Wu, Xiaosong; Wei, Bo; Chen, Lin

2017-04-26

Ring finger protein 43 (RNF43) is a member of the transmembrane E3 ubiquitin ligase family that was originally found in stem cells and plays important roles in tumor formation and progression. Our previous study indicated that RNF43 might be a tumor suppressor protein in gastric cancer. Given its antagonistic relationship with leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), one of the gastric cancer stem cell markers, investigation of the potential role of RNF43 in gastric stem cancer cells is necessary. Immunohistochemistry staining, western blot analysis, and quantitative reverse transcription polymerase chain reaction were used to determine the mRNA and protein expression level of RNF43 and other Wnt pathway factors. Gastric cancer stem-like cells were obtained from gastric cancer tumor and cell lines by tumorsphere culture. The adeno-associated virus system was used to upregulate RNF43 expression in cancer cells. Functional experiments including tumorsphere formation, chemotherapy resistance, surface marker detection, and tumor xenograft assay were performed to measure stem-like properties in gastric cancer stem-like cells after RNF43 overexpression. RNF43 loss was significantly associated with TNM stage, distant metastasis, and Lauren classification, and predicted worse prognosis in gastric cancer patients. RNF43 expression was even lower in tumorspheres derived from tumor tissues or cell lines compared with adherent cancer cells and normal gastric cells. Overexpression of RNF43 in gastric cancer cells impaired their stem-like properties, including sphere formation ability, chemoresistance in vitro, and tumorigenicity in vivo. Moreover, Wnt pathway-related proteins were decreased in RNF43-overexpressing cells, while Wnt pathway activators could reverse the trend to some extent. Our findings indicated that RNF43 might not only participate in gastric cancer progression, but also attenuate the stemness of gastric cancer stem-like cells through

Risk Factors of Atrophic Gastritis and Intestinal Metaplasia in First-Degree Relatives of Gastric Cancer Patients Compared with Age-Sex Matched Controls

PubMed Central

Oh, Sooyeon; Kim, Nayoung; Yoon, Hyuk; Choi, Yun Jin; Lee, Ju Yup; Park, Kyoung Jun; Kim, Hee Jin; Kang, Kyu Keun; Oh, Dong Hyun; Seo, A Young; Lee, Jae Woo; Shin, Cheol Min; Park, Young Soo; Oh, Jane C.; Lee, Dong Ho; Jung, Hyun Chae

2013-01-01

Background: To identify whether first-degree relatives (FDRs) of gastric cancer (GC) patients have increased risk for atrophic gastritis (AG) and intestinal metaplasia (IM) in relation to other risk factors of GC. Methods: The study cohort consisted of 224 pairs of age-sex matched controls and FDRs. AG and IM in the gastric mucosa were scored histologically using the updated Sydney classification. Risk of having AG and IM was studied by comparing FDRs to controls. Impacts of age, H. pylori infection, smoking, dietary and socioeconomic factors on the presence of AG and IM were studied. Results: In multivariate regression analysis, FDRs had adjusted OR of 2.69 (95% CI 1.06–6.80, P=0.037) for antral IM in male population. Adjusted OR for antral AG and IM were 9.28 (95% CI 4.73–18.18, P<0.001) and 7.81 (95% CI 3.72–16.40, P<0.001) for the H. pylori infected subjects in total population. Getting old by 5 years increased the ORs of having AG and IM by approximately 1.25 fold (P<0.001). Spicy food increased the OR of antral IM by 2.28 fold (95% CI 1.36–3.84, P=0.002). Conclusions: Family history of GC was an independent risk factor for antral IM in male in our study, which could be one reason for the increase of gastric cancer in the family member of gastric cancer. It could be an evidence for the necessity of frequent endoscopy in the presence of family history of GC compared to general population in male. PMID:25337541

Surgical resection of late solitary locoregional gastric cancer recurrence in stomach bed.

PubMed

Watanabe, Masanori; Suzuki, Hideyuki; Maejima, Kentaro; Komine, Osamu; Mizutani, Satoshi; Yoshino, Masanori; Bo, Hideki; Kitayama, Yasuhiko; Uchida, Eiji

2012-07-01

Late-onset and solitary recurrence of gastric signet ring cell (SRC) carcinoma is rare. We report a successful surgical resection of late solitary locoregional recurrence after curative gastrectomy for gastric SRC carcinoma. The patient underwent total gastrectomy for advanced gastric carcinoma at age 52. Seven years after the primary operation, he visited us again with sudden onset of abdominal pain and vomiting. We finally decided to perform an operation, based on a diagnosis of colon obstruction due to the recurrence of gastric cancer by clinical findings and instrumental examinations. The laparotomic intra-abdominal findings showed that the recurrent tumor existed in the region surrounded by the left diaphragm, colon of splenic flexure, and pancreas tail. There was no evidence of peritoneal dissemination, and peritoneal lavage fluid cytology was negative. We performed complete resection of the recurrent tumor with partial colectomy, distal pancreatectomy, and partial diaphragmectomy. Histological examination of the resected specimen revealed SRC carcinoma, identical in appearance to the previously resected gastric cancer. We confirmed that the intra-abdominal tumor was a locoregional gastric cancer recurrence in the stomach bed. The patient showed a long-term survival of 27 months after the second operation. In the absence of effective alternative treatment for recurrent gastric carcinoma, surgical options should be pursued, especially for late and solitary recurrence.

Environmental and lifestyle risk factors of gastric cancer.

PubMed

Lee, Yeong Yeh; Derakhshan, Mohammad H

2013-06-01

Effective prevention and early diagnostic strategies are the most important public health interventions in gastric cancer, which remains a common malignancy worldwide. Preventive strategies require identification and understanding of environmental risk factors that lead to carcinogenesis. Helicobacter pylori (H. pylori) is the primary carcinogen as this ancient bacterium has a complex ability to interact with its human host. Smoking and salt are strong independent risk factors for gastric cancer whereas alcohol is only a risk when it is heavily consumed. Red meat and high fat increase the risk of gastric cancer however fresh fruits, vegetables (allium family) and certain micronutrients (selenium, vitamin C) reduce the risk, with evidence lacking for fish, coffee and tea. Foods that inhibit H. pylori viability, colonization and infection may reduce cancer risk. Obesity is increasingly recognized as a contributory factor in gastric cardia carcinogenesis. Therefore, modest daily physical activities can be protective against cancer. Foundry workers are at risk for developing gastric cancer with dust iron being an important cause. Other risk factors include Epstein-Barr virus (EBV), possibly JC virus and radiation but the effects of these are likely to remain small.

The role of leptin in gastric cancer: Clinicopathologic features and molecular mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Kang Nyeong; Choi, Ho Soon, E-mail: hschoi96@hanyang.ac.kr; Yang, Sun Young

Highlights: • Leptin and Ob-R are expressed in gastric adenoma and early and advanced cancer. • Leptin is more likely associated with differentiated gastric cancer or cardia cancer. • Leptin proliferates gastric cancer cells via activating the STAT3 and ERK1/2 pathways. - Abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastricmore » adenoma (n = 38), early gastric cancer (EGC) (n = 38), and advanced gastric cancer (AGC) (n = 38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.« less

The descriptive epidemiology of gastric cancer in Central America and comparison with United States Hispanic populations.

PubMed

Corral, Juan E; Delgado Hurtado, Juan J; Domínguez, Ricardo L; Valdez de Cuéllar, Marisabel; Balmore Cruz, Carlos; Morgan, Douglas R

2015-03-01

The aims of this study were to delineate the epidemiology of gastric adenocarcinoma in Central America and contrast it with Hispanic-Latino populations in the USA. Published literature and Central America Ministry of Health databases were used as primary data sources, including national, population-based, and hospital-based registries. US data was obtained from the National Cancer Institute (NCI)-Epidemiology End Results Program (SEER) registry. Incident gastric adenocarcinoma cases were analyzed for available data between 1985 and 2011, including demographic variables and pathology information. In Central America, 19,741 incident gastric adenocarcinomas were identified. Two thirds of the cases were male, 20.5 % were under age 55, and 58.5 %were from rural areas. In the SEER database (n = 7871), 57.8 % were male and 28.9 % were under age 55. Among the US Hispanics born in Central America with gastric cancer (n = 1210), 50.3 % of cases were male and 38.1 % were under age 55. Non-cardia gastric cancer was more common in Central America (83.3 %), among US Hispanics (80.2 %), and Hispanics born in Central America (86.3 %). Cancers of the antrum were more common in Central America (73.6 %), whereas cancers of the corpus were slightly more common among US Hispanics (54.0 %). Adenocarcinoma of the diffuse subtype was relatively common, both in Central America (35.7 %) and US Hispanics (69.5 %), although Lauren classification was reported in only 50 % of cases. A significant burden of gastric adenocarcinoma is observed in Central America based upon limited available data. Differences are noted between Central America and US Hispanics. Strengthening population-based registries is needed for improved cancer control in Central America, which may have implications for the growing US Hispanic population.

[Experience and present situation of Western China Gastric Cancer Collaboration].

PubMed

Hu, Jiankun; Zhang, Weihan; Western China Gastric Cancer Collaboration, China

2017-03-25

The Western China Gastric Cancer Collaboration (WCGCC) was founded in Chongqing, China in 2011. At the early stage of the collaboration, there were only about 20 centers. While now, there are 36 centers from western area of China, including Sichuan, Chongqing, Yunnan, Shanxi, Guizhou, Gansu, Qinghai, Xinjiang, Ningxia and Tibet. During the past few years, the WCGCC organized routinely gastric cancer standardized treatment tours, training courses of mini-invasive surgical treatment of gastric cancer and the clinical research methodology for members of the collaboration. Meanwhile, the WCGCC built a multicenter database of gastric cancer since 2011 and the entering and management refer to national gastric cancer registration entering system of Japan Gastric Cancer Association. During the entering and collection of data, 190 items of data have unified definition and entering standard from Japan Gastric Cancer Guidelines. Nowadays, this database included about 11 872 gastric cancer cases, and in this paper we will introduce the initial results of these cases. Next, the collaboration will conduct some retrospective studies based on this database to analyze the clinicopathological characteristics of patients in the western area of China. Besides, the WCGCC performed a prospective study, also. The first randomized clinical trial of the collaboration aims to compare the postoperative quality of life between different reconstruction methods for total gastrectomy(WCGCC-1202, ClinicalTrials.gov Identifier: NCT02110628), which began in 2015, and now this study is in the recruitment period. In the next steps, we will improve the quality of the database, optimize the management processes. Meanwhile, we will engage in more exchanges and cooperation with the Chinese Cochrane Center, reinforce the foundation of the clinical trials research methodology. In aspect of standardized surgical treatment of gastric cancer, we will further strengthen communication with other international

The Changing Face of Noncardia Gastric Cancer Incidence Among US Non-Hispanic Whites.

PubMed

Anderson, William F; Rabkin, Charles S; Turner, Natalie; Fraumeni, Joseph F; Rosenberg, Philip S; Camargo, M Constanza

2018-01-19

The initial step for noncardia gastric carcinogenesis is atrophic gastritis, driven by either Helicobacter pylori infection or autoimmunity. In recent decades, the prevalence rates of these two major causes declined and increased, respectively, with changes in Western lifestyles. We therefore assessed gastric cancer incidence trends for US race/ethnic groups, 1995-2013. Age-standardized rates (ASRs) from 45 North American Association of Central Cancer Tumor Registries were summarized by estimated annual percentage change (EAPC) and 95% confidence intervals (CIs). Age period cohort models supplemented standard descriptive techniques and projected future trends. There were 137 447 noncardia cancers in 4.4 billion person-years of observation. Among non-Hispanic whites, the ASR was 2.2 per 100 000 person-years, with an EAPC of -2.3% (95% CI = -2.0% to -2.6%). Notwithstanding this overall decline, EAPCs rose 1.3% (95% CI = 0.6% to 2.1%) for persons younger than age 50 years and fell -2.6% (95% CI = -2.4% to -2.9%) for older individuals. These converging trends manifested a birth cohort effect more pronounced among women than men, with incidence among women born in 1983 twofold (95% CI = 1.1-fold to 3.6-fold) greater than those born in 1951. Age interaction was also statistically significant among Hispanic whites, with slightly increasing vs decreasing EAPCs for younger and older individuals, respectively. Incidence declined regardless of age for other races. Current trends foreshadow expected reversals in both falling incidence and male predominance among non-Hispanic whites. Dysbiosis of the gastric microbiome associated with modern living conditions may be increasing risk of autoimmune gastritis and consequent noncardia cancer. The changing face by age and sex of gastric cancer warrants analytical studies to identify potential causal mechanisms. Published by Oxford University Press 2018. This work is written by US Government employees and is in the public

Towards personalized perioperative treatment for advanced gastric cancer

PubMed Central

Miao, Ru-Lin; Wu, Ai-Wen

2014-01-01

Gastric cancer is one of the most frequently diagnosed cancers worldwide. Although the rate of gastric cancer has declined dramatically over the past decades in most developed Western countries, it has not declined in East Asia. Currently, a radical gastrectomy is still the only curative treatment for gastric cancer. Over the last twenty years, however, surgery alone has been replaced by a multimodal perioperative approach. To achieve the maximum benefit from the perioperative treatment, a thorough evaluation of the tumor must first be performed. A complete assessment of gastric cancer is divided into two parts: staging and histology. According to the stage and histology of the cancer, perioperative chemotherapy or radiochemotherapy can be implemented, and perioperative targeted therapies such as trastuzumab may also play a role in this field. However, perioperative treatment approaches have not been widely accepted until a series of clinical trials were performed to evaluate the value of perioperative treatment. Although multimodal perioperative treatment has been widely applied in clinical practice, personalization of perioperative treatment represents the next stage in the treatment of gastric cancer. Genomic-guided treatment and efficacy prediction using molecular biomarkers in perioperative treatment are of great importance in the evolution of treatment and may become an ideal treatment method. PMID:25206266

New agents on the horizon in gastric cancer.

PubMed

Lordick, F; Shitara, K; Janjigian, Y Y

2017-08-01

Conventional cytotoxic chemotherapy has been the backbone of advanced gastric cancer treatment for decades and still represents a key element of the therapeutic armamentarium. However, only small increments in survival outcomes have been reached. A better understanding of genetic alterations and molecular signatures of gastric cancer has been reached in the last years. It will serve as a roadmap for better treatment stratification and future drug development. We reviewed preclinical and clinical studies that assessed novel treatment targets and emerging drug therapies in gastric cancer. We performed research via PubMed, and the congress webpages of the American Society of Clinical Oncology, European Society of Medical Oncology and the Japanese Society of Medical Oncology. HER2-targeting with trastuzumab is effective in HER2-positive metastatic gastric cancer; combined HER2 targeting strategies are being investigated. Studies assessing the role of HER2 targeting in the perioperative setting are ongoing. Novel treatment targets include inhibition of cancer stemness-related signaling pathways like STAT3. DNA damage repair and Claudin 18.2, a tight junction protein with high expression in gastric cancers are also novel molecular drug targets. Modification of the tumor microenvironment, including activation of immune response by PD-1/PD-L1 checkpoint inhibitors and stroma modification by matrix metalloproteinase-9 inhibition, led to first promising treatment results. Novel treatment options for gastric cancer patients are emerging. They involve novel mechanisms of action, and are based on our constantly increasing understanding of tumor biology and better molecular stratification of gastric cancer patients. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The predictive factors for lymph node metastasis in early gastric cancer: A clinical study.

PubMed

Wang, Yinzhong

2015-01-01

To detect the clinicopathological factors associated with lymph node metastases in early gastric cancer. We retrospectively evaluated the distribution of metastatic nodes in 198 patients with early gastric cancer treated in our hospital between May 2008 and January 2015, the clinicopathological factors including age, gender, tumor location, tumor size, macroscopic type, depth of invasion, histological type and venous invasion were studied, and the relationship between various parameters and lymph node metastases was analyzed. In this study, one hundred and ninety-eight patients with early gastric cancer were included, and lymph node metastasis was detected in 28 patients. Univariate analysis revealed a close relationship between tumor size, depth of invasion, histological type, venous invasion, local ulceration and lymph node metastases. Multivariate analysis revealed that the five factors were independent risk factors for lymph node metastases. The clinicopathological parameters including tumor size, depth of invasion, local ulceration, histological type and venous invasion are closely correlated with lymph node metastases, should be paid high attention in early gastric cancer patients.

Current molecular markers for gastric progenitor cells and gastric cancer stem cells.

PubMed

Qiao, Xiaotan T; Gumucio, Deborah L

2011-07-01

Gastric stem and progenitor cells (GPC) play key roles in the homeostatic renewal of gastric glands and are instrumental in epithelial repair after injury. Until very recently, the existence of GPC could only be inferred by indirect labeling strategies. The last few years have seen significant progress in the identification of biomarkers that allow prospective identification of GPC. The analysis of these unique cell populations is providing new insights into the molecular underpinnings of gastric epithelial homeostasis and repair. Of closely related interest is the potential to identify so-called cancer stem cells, a rare subpopulation of tumor-initiating cells. Here, we review the current useful biomarkers for GPC, including: (a) those that have been demonstrated by lineage tracing to give rise to all gastric cell lineages (e.g., the villin-transgene marker as well as Lgr5); (b) those that give rise to a subset of gastric lineages (e.g., TFF2); (c) markers that recognize cryptic progenitors for metaplasia (e.g., MIST1), and (d) markers that have not yet been analyzed by lineage tracing (e.g., DCKL1/DCAMKL1, CD133/PROM1, and CD44). The study of these markers has been mostly limited to the mouse model, but the hope is that the rapid pace of recent breakthroughs in this animal model will soon lead to a greater understanding of human gastric stem cell biology and to new insights into gastric cancer, the second leading cause of cancer-related death worldwide.

Local resection of the stomach for gastric cancer.

PubMed

Kinami, Shinichi; Funaki, Hiroshi; Fujita, Hideto; Nakano, Yasuharu; Ueda, Nobuhiko; Kosaka, Takeo

2017-06-01

The local resection of the stomach is an ideal method for preventing postoperative symptoms. There are various procedures for performing local resection, such as the laparoscopic lesion lifting method, non-touch lesion lifting method, endoscopic full-thickness resection, and laparoscopic endoscopic cooperative surgery. After the invention and widespread use of endoscopic submucosal dissection, local resection has become outdated as a curative surgical technique for gastric cancer. Nevertheless, local resection of the stomach in the treatment of gastric cancer in now expected to make a comeback with the clinical use of sentinel node navigation surgery. However, there are many issues associated with local resection for gastric cancer, other than the normal indications. These include gastric deformation, functional impairment, ensuring a safe surgical margin, the possibility of inducing peritoneal dissemination, and the associated increase in the risk of metachronous gastric cancer. In view of these issues, there is a tendency to regard local resection as an investigative treatment, to be applied only in carefully selected cases. The ideal model for local resection of the stomach for gastric cancer would be a combination of endoscopic full-thickness resection of the stomach using an ESD device and hand sutured closure using a laparoscope or a surgical robot, for achieving both oncological safety and preserved functions.

Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer.

PubMed

Yang, Yunben; Shao, Yongfu; Zhu, Mengying; Li, Qier; Yang, Fang; Lu, Xuwen; Xu, Chunjing; Xiao, Bingxiu; Sun, Yanke; Guo, Junming

2016-01-01

Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.

Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer.

PubMed

Choi, Il Ju; Kook, Myeong-Cherl; Kim, Young-Il; Cho, Soo-Jeong; Lee, Jong Yeul; Kim, Chan Gyoo; Park, Boram; Nam, Byung-Ho

2018-03-22

Patients with early gastric cancers that are limited to gastric mucosa or submucosa usually have an advanced loss of mucosal glandular tissue (glandular atrophy) and are at high risk for subsequent (metachronous) development of new gastric cancer. The long-term effects of treatment to eradicate Helicobacter pylori on histologic improvement and the prevention of metachronous gastric cancer remain unclear. In this prospective, double-blind, placebo-controlled, randomized trial, we assigned 470 patients who had undergone endoscopic resection of early gastric cancer or high-grade adenoma to receive either H. pylori eradication therapy with antibiotics or placebo. Two primary outcomes were the incidence of metachronous gastric cancer detected on endoscopy performed at the 1-year follow-up or later and improvement from baseline in the grade of glandular atrophy in the gastric corpus lesser curvature at the 3-year follow-up. A total of 396 patients were included in the modified intention-to-treat analysis population (194 in the treatment group and 202 in placebo group). During a median follow-up of 5.9 years, metachronous gastric cancer developed in 14 patients (7.2%) in the treatment group and in 27 patients (13.4%) in the placebo group (hazard ratio in the treatment group, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.03). Among the 327 patients in the subgroup that underwent histologic analysis, improvement from baseline in the atrophy grade at the gastric corpus lesser curvature was observed in 48.4% of the patients in the treatment group and in 15.0% of those in the placebo group (P<0.001). There were no serious adverse events; mild adverse events were more common in the treatment group (42.0% vs. 10.2%, P<0.001). Patients with early gastric cancer who received H. pylori treatment had lower rates of metachronous gastric cancer and more improvement from baseline in the grade of gastric corpus atrophy than patients who received placebo. (Funded by the National

Gastric cancer presenting with solitary gigantic pelvic metastasis.

PubMed

Zheng, Qi; Nan, Kejun; Yao, Yu

2012-07-01

Bone metastasis of gastric cancer is relatively uncommon in clinical practice. Moreover, it is all the more unusual for the primary presentation of gastric malignancy to be bone metastasis. Here, we describe a male patient who complained of pain and edema in his right lower extremity. Further assessment by computed tomography and positron emission tomography revealed an abnormally thickened gastric cardia and a giant neoplasm in the right pelvis with bone damage. Consequently, the finding of adenocarcinoma cells in pelvic and cardia biopsy specimens contributed to the diagnosis of pelvic metastasis from gastric cancer. This case report illustrates that stomach cancer has the potential, although far less than breast, prostate and lung cancers, to metastasize to bone. In addition, it highlights the peculiarity of this bone metastasis which is pelvic, solitary and huge.

Prevention of Gastric Cancer: Eradication of Helicobacter pylori and Beyond

PubMed Central

Tsukamoto, Tetsuya; Nakagawa, Mitsuru; Kiriyama, Yuka; Toyoda, Takeshi; Cao, Xueyuan

2017-01-01

Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents. PMID:28771198

Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives.

PubMed

Choi, Yoon Young; Noh, Sung Hoon; Cheong, Jae-Ho

2016-01-01

Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus-positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

Stomach (Gastric) Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

For stomach (gastric) cancer, there is no standard or routine screening test for the general U.S. population. Review the evidence on the benefits and harms of screening for gastric cancer using barium-meal photofluorography, gastric endoscopy, or serum pepsinogen in this expert-reviewed summary.

Identifying therapeutic targets in gastric cancer: the current status and future direction

PubMed Central

Yu, Beiqin; Xie, Jingwu

2016-01-01

Gastric cancer is the third leading cause of cancer-related death worldwide. Our basic understanding of gastric cancer biology falls behind that of many other cancer types. Current standard treatment options for gastric cancer have not changed for the last 20 years. Thus, there is an urgent need to establish novel strategies to treat this deadly cancer. Successful clinical trials with Gleevec in CML and gastrointestinal stromal tumors have set up an example for targeted therapy of cancer. In this review, we will summarize major progress in classification, therapeutic options of gastric cancer. We will also discuss molecular mechanisms for drug resistance in gastric cancer. In addition, we will attempt to propose potential future directions in gastric cancer biology and drug targets. PMID:26373844

Incidence of metachronous gastric cancer in the remnant stomach after synchronous multiple cancer surgery.

PubMed

Nozaki, Isao; Hato, Shinji; Kobatake, Takaya; Ohta, Koji; Kubo, Yoshirou; Nishimura, Rieko; Kurita, Akira

2014-01-01

In the preoperative evaluation for gastric cancer, high-resolution endoscopic technologies allow us to detect small accessory lesions. However, it is not known if the gastric remnant after partial gastrectomy for synchronous multiple gastric cancers has a greater risk for metachronous cancer. The purpose of this study was to determine the incidence of metachronous cancer in this patient subset compared with that after solitary cancer surgery. Data on a consecutive series of 1,281 patients gastrectomized for early gastric cancer from 1991 to 2007 were analyzed retrospectively. The 715 gastric remnants after distal gastrectomy were periodically surveyed by endoscopic examination in Shikoku Cancer Center. Among those surveyed cases, 642 patients were pathologically diagnosed with solitary lesion (SO group) and 73 patients with synchronous multiple lesions (MU group) at the time of the initial surgery. In the follow-up period, 15 patients in the SO group and 3 patients in the MU group were diagnosed as having metachronous cancer in the gastric remnant. The cumulative 4-year incidence rate was 1.9 % in the SO group and 5.5 % in the MU group. The difference did not reach the significant level by the log-rank test. The incidence of metachronous cancer is higher after multiple cancer surgery; however, the difference is not statistically significant.

Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.

PubMed

Fitzgerald, Rebecca C; Hardwick, Richard; Huntsman, David; Carneiro, Fatima; Guilford, Parry; Blair, Vanessa; Chung, Daniel C; Norton, Jeff; Ragunath, Krishnadath; Van Krieken, J Han; Dwerryhouse, Sarah; Caldas, Carlos

2010-07-01

25-30% of families fulfilling the criteria for hereditary diffuse gastric cancer have germline mutations of the CDH1 (E-cadherin) gene. In light of new data and advancement of technologies, a multidisciplinary workshop was convened to discuss genetic testing, surgery, endoscopy and pathology reporting. The updated recommendations include broadening of CDH1 testing criteria such that: histological confirmation of diffuse gastric criteria is only required for one family member; inclusion of individuals with diffuse gastric cancer before the age of 40 years without a family history; and inclusion of individuals and families with diagnoses of both diffuse gastric cancer (including one before the age of 50 years) and lobular breast cancer. Testing is considered appropriate from the age of consent following counselling and discussion with a multidisciplinary team. In addition to direct sequencing, large genomic rearrangements should be sought. Annual mammography and breast MRI from the age of 35 years is recommended for women due to the increased risk for lobular breast cancer. In mutation positive individuals prophylactic total gastrectomy at a centre of excellence should be strongly considered. Protocolised endoscopic surveillance in centres with endoscopists and pathologists experienced with these patients is recommended for: those opting not to have gastrectomy, those with mutations of undetermined significance, and in those families for whom no germline mutation is yet identified. The systematic histological study of prophylactic gastrectomies almost universally shows pre-invasive lesions including in situ signet ring carcinoma with pagetoid spread of signet ring cells. Expert histopathological confirmation of these early lesions is recommended.

Companion diagnostics for the targeted therapy of gastric cancer.

PubMed

Yoo, Changhoon; Park, Young Soo

2015-10-21

Gastric cancer is the fourth most common type of cancer and represents a major cause of cancer-related deaths worldwide. With recent biomedical advances in our understanding of the molecular characteristics of gastric cancer, many genetic alterations have been identified as potential targets for its treatment. Multiple novel agents are currently under development as the demand for active agents that improve the survival of gastric cancer patients constantly increases. Based on lessons from previous trials of targeted agents, it is now widely accepted that the establishment of an optimal diagnostic test to select molecularly defined patients is of equal importance to the development of active agents against targetable genetic alterations. Herein, we highlight the current status and future perspectives of companion diagnostics in the treatment of gastric cancer.

Gastric cancer in FAP: a concerning rise in incidence.

PubMed

Mankaney, Gautam; Leone, Pamela; Cruise, Michael; LaGuardia, Lisa; O'Malley, Margaret; Bhatt, Amit; Church, James; Burke, Carol A

2017-07-01

The highest cancer risks in familial adenomatous polyposis (FAP) include colorectal, duodenal, and thyroid for which surveillance is recommended. Nearly all patients with FAP have gastric fundic gland polyposis (FGP), but gastric cancers are rarely reported with a similar incidence as the general population. We describe a recent, sudden increase in the incidence of gastric cancer in FAP. Seven of the ten cases were diagnosed in the last 20 months. Comparing our population to the SEER database for gastric cancer, the standardized incidence ratio is 140. All cases arose in patients with a carpeting of FGP and associated with large mounds of proximal gastric polyps. Nearly all patients were under upper endoscopic surveillance. This is a concerning observation and reflects a change in the phenotypic presentation of FAP in Western patients.

How to stomach an epigenetic insult: the gastric cancer epigenome.

PubMed

Padmanabhan, Nisha; Ushijima, Toshikazu; Tan, Patrick

2017-08-01

Gastric cancer is a deadly malignancy afflicting close to a million people worldwide. Patient survival is poor and largely due to late diagnosis and suboptimal therapies. Disease heterogeneity is a substantial obstacle, underscoring the need for precision treatment strategies. Studies have identified different subgroups of gastric cancer displaying not just genetic, but also distinct epigenetic hallmarks. Accumulating evidence suggests that epigenetic abnormalities in gastric cancer are not mere bystander events, but rather promote carcinogenesis through active mechanisms. Epigenetic aberrations, induced by pathogens such as Helicobacter pylori, are an early component of gastric carcinogenesis, probably preceding genetic abnormalities. This Review summarizes our current understanding of the gastric cancer epigenome, highlighting key advances in recent years in both tumours and pre-malignant lesions, made possible through targeted and genome-wide technologies. We focus on studies related to DNA methylation and histone modifications, linking these findings to potential therapeutic opportunities. Lessons learned from the gastric cancer epigenome might also prove relevant for other gastrointestinal cancers.

MicroRNA-650 targets ING4 to promote gastric cancer tumorigenicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, XueLi, E-mail: zhangxueli.200010@yahoo.com.cn; Zhu, WeiYing; Zhang, JiFa

2010-04-30

MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of target mRNAs. Altered expression of specific miRNAs in human gastric cancer progression has been reported; however, the role of miR-650 in gastric cancer is poorly understood. In this study, we show that miR-650 is involved in lymphatic and distant metastasis in human gastric cancer, and we find that ectopic expression of miR-650 promotes tumorigenesis and proliferation of gastric cancer cells. A luciferase reporter assay demonstrates that Inhibitor of Growth 4 (ING4) is a direct target of miR-650. Collectively, our study demonstrates that over-expression of miR-650 in gastric cancer may promotemore » proliferation and growth of cancer cells, at least partially through directly targeting ING4. These findings help clarify the molecular mechanisms involved in gastric carcinogenesis and indicate that miR-650 modulation may be a bona fide miRNA-based treatment of gastric cancer.« less

AMPKα Modulation in Cancer Progression: Multilayer Integrative Analysis of the Whole Transcriptome in Asian Gastric Cancer

PubMed Central

Cho, Jae Yong; Cheong, Jae-Ho; Kim, Hoguen; Li, Min; Downey, Thomas J.; Dyer, Matthew D.; Sun, Yongming; Sun, Jingtao; Beasley, Ellen M.; Chung, Hyun Cheol; Noh, Sung Hoon; Weinstein, John N.; Liu, Chang-Gong; Powis, Garth

2013-01-01

Gastric cancer is the most common cancer in Asia and most developing countries. Despite the use of multimodality therapeutics, it remains the second leading cause of cancer death in the world. To identify the molecular underpinnings of gastric cancer in the Asian population, we applied an RNA-sequencing approach to gastric tumor and noncancerous specimens, generating 680 million informative short reads to quantitatively characterize the entire transcriptome of gastric cancer (including mRNAs and microRNAs). A multi-layer analysis was then developed to identify multiple types of transcriptional aberrations associated with different stages of gastric cancer, including differentially expressed mRNAs, recurrent somatic mutations and key differentially expressed microRNAs. Through this approach, we identified the central metabolic regulator AMPK-α as a potential functional target in Asian gastric cancer. Further, we experimentally demonstrated the translational relevance of this gene as a potential therapeutic target for early-stage gastric cancer in Asian patients. Together, our findings not only provide a valuable information resource for identifying and elucidating the molecular mechanisms of Asian gastric cancer, but also represent a general integrative framework to develop more effective therapeutic targets. PMID:22434430

Essential role of gastric gland mucin in preventing gastric cancer in mice

PubMed Central

Karasawa, Fumitoshi; Shiota, Akira; Goso, Yukinobu; Kobayashi, Motohiro; Sato, Yoshiko; Masumoto, Junya; Fujiwara, Maiko; Yokosawa, Shuichi; Muraki, Takashi; Miyagawa, Shinichi; Ueda, Masatsugu; Fukuda, Michiko N.; Fukuda, Minoru; Ishihara, Kazuhiko; Nakayama, Jun

2012-01-01

Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Previously, we identified human α1,4-N-acetylglucosaminyltransferase (α4GnT), which is responsible for the O-glycan biosynthesis and characterized αGlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt–/– mice to better understand its role in vivo. A4gnt–/– mice showed complete lack of αGlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence in the absence of H. pylori infection. Microarray and quantitative RT-PCR analysis revealed upregulation of genes encoding inflammatory chemokine ligands, proinflammatory cytokines, and growth factors, such as Ccl2, Il-11, and Hgf in the gastric mucosa of A4gnt–/– mice. Further supporting an important role for this O-glycan in cancer progression, we also observed significantly reduced αGlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of αGlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, αGlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation. PMID:22307328

[Clinical trials of laparoscopic gastric cancer surgery in South Korea: review and prospect].

PubMed

Zhu, Chunchao; Zhao, Gang; Cao, Hui

2018-02-25

Laparoscopic technology is gradually accepted in gastric cancer surgery, whose efficacy has been demonstrated by some clinical researches. Randomized controlled trials (RCT) are considered as the most important evidence to prove clinical outcomes of laparoscopic surgery for gastric cancer. Korean gastric surgeons have made great contributions to RCT in laparoscopic gastric cancer surgery. KLASS (Korean Laparoscopic Gastrointestinal Surgery Study Group) is one of the most important forerunner and global leader of clinical trials of gastric cancer treatment. KLASS series clinical trials are attracting global attention because of the significant value of surgical treatment for gastric cancer. The RCTs in Korea involve in many aspects of laparoscopic gastrectomy for gastric cancer, including laparoscopy application in early gastric cancer (KLASS-01, KLASS-03 and KLASS-07), advanced gastric cancer (KLASS-02 and KLASS-06), function-preserving gastrectomy (KLASS-04,KLASS-05) and sentinel node navigation surgery (SENORITA trial). In order to share some informations of these RCTs, we review and prospect some important clinical trials of laparoscopic gastric cancer surgery in Korea. With the experience of Korean gastric surgeons, we can make more progress in our own clinical trials of laparoscopic gastric cancer surgery.

Pathohistological classification systems in gastric cancer: Diagnostic relevance and prognostic value

PubMed Central

Berlth, Felix; Bollschweiler, Elfriede; Drebber, Uta; Hoelscher, Arnulf H; Moenig, Stefan

2014-01-01

Several pathohistological classification systems exist for the diagnosis of gastric cancer. Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics, disease specific criteria and overall outcome. It is still controversial as to which classification system imparts the most reliable information, and therefore, the choice of system may vary in clinical routine. In addition to the most common classification systems, such as the Laurén and the World Health Organization (WHO) classifications, other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients. In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer, there is no sole classification system that is consistently used worldwide in diagnostics and research. However, several national guidelines for the treatment of gastric cancer refer to the Laurén or the WHO classifications regarding therapeutic decision-making, which underlines the importance of a reliable classification system for gastric cancer. The latest results from gastric cancer studies indicate that it might be useful to integrate DNA- and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance. This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer. PMID:24914328

TCGA divides gastric cancer into four molecular subtypes: implications for individualized therapeutics.

PubMed

Zhang, Wei

2014-10-01

Gastric cancer is a leading cause of cancer deaths in the world. The treatment of gastric cancer is challenging because of its highly heterogeneous etiology and clinical characteristics. Recent genomic and molecular characterization of gastric cancer, especially the findings reported by the Cancer Genome Atlas (TCGA), have shed light on the heterogeneity and potential targeted therapeutics for four different subtypes of gastric cancer.

Clinical significance of lymph node metastasis in gastric cancer

PubMed Central

Deng, Jing-Yu; Liang, Han

2014-01-01

Gastric cancer, one of the most common malignancies in the world, frequently reveals lymph node, peritoneum, and liver metastases. Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection, which results in poor prognosis. Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer. Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials, it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year follow-up study. Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide, but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis. It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer. Besides, the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer. PMID:24744586

Helicobacter pylori serological biomarkers of gastric cancer risk in the MCC-Spain case-control Study.

PubMed

Fernández de Larrea-Baz, Nerea; Pérez-Gómez, Beatriz; Michel, Angelika; Romero, Beatriz; Lope, Virginia; Pawlita, Michael; Fernández-Villa, Tania; Moreno, Victor; Martín, Vicente; Willhauck-Fleckenstein, Martina; López-Abente, Gonzalo; Castilla, Jesús; Fernández-Tardón, Guillermo; Dierssen-Sotos, Trinidad; Santibáñez, Miguel; Peiró, Rosana; Jiménez-Moleón, José Juan; Navarro, Carmen; Castaño-Vinyals, Gemma; Kogevinas, Manolis; Pollán, Marina; de Sanjosé, Silvia; Del Campo, Rosa; Waterboer, Tim; Aragonés, Nuria

2017-10-01

Helicobacter pylori infection is one of the main risk factors for non-cardia gastric cancer. However, only a minority of infected persons develop the disease. This study aims at identifying H. pylori related serological biomarkers of risk for gastric cancer. Incident gastric cancer cases and population controls (age, sex and region frequency-matched) from the MCC-Spain multicase-control Study were included. Seroreactivities against 16H. pylori proteins were determined using multiplex serology. Infection was defined as seropositivity against≥4 proteins. Relation of serological results to non-cardia and cardia gastric cancer was assessed using multivariable mixed logistic regression and principal components analysis. Seroprevalence was 88% among 2071 controls, 95% among 202 non-cardia gastric cancer cases (OR=1.9 (95% CI: 1.0-3.6)) and 85% among 62 cardia cancer cases (OR=0.5 (95% CI: 0.3-1.1)). In infected subjects, seropositivity for UreA, HP231, NapA and Cagδ was associated with lower non-cardia gastric cancer risk, while seropositivity for CagA and VacA was associated with higher risk. Seropositivity for CagA and seronegativity for Cagδ maintained the association after additional adjustment by serostatus of significant proteins. We identified two antibody reactivity patterns: the "virulent-pattern", related to a threefold higher risk of non-cardia gastric cancer and the "non-virulent pattern", related to a 60% decreased risk (4th vs. first quartile). In our population, people seropositive for H. pylori were characterized by two patterns of antibody reactivity against H. pylori proteins: 1) Combined high seroreactivity against several proteins, associated with a lower non-cardia gastric cancer risk, and 2) High seroreactivity against CagA and VacA, associated with an increased risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines

PubMed Central

Calcagno, Danielle Queiroz; Takeno, Sylvia Santomi; Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Wisnieski, Fernanda; Chen, Elizabeth Suchi; Araújo, Taíssa Maíra Thomaz; Lima, Eleonidas Moura; Melaragno, Maria Isabel; Demachki, Samia; Assumpção, Paulo Pimentel; Burbano, Rommel Rodriguez; Smith, Marília Cardoso

2016-01-01

AIM To identify common copy number alterations on gastric cancer cell lines. METHODS Four gastric cancer cell lines (ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis. RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha (IL11RA) and maternal embryonic leucine zipper kinase (MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11RA and MELK was observed in 19.1% (13/68) and 55.9% (38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer. PMID:27920471

Cthrc1 overexpression is an independent prognostic marker in gastric cancer.

PubMed

Gu, Lina; Liu, Lei; Zhong, Lili; Bai, Yuxian; Sui, Hong; Wei, Xiaoli; Zhang, Wenjie; Huang, Peng; Gao, Dandan; Kong, Ying; Lou, Ge

2014-05-01

Collagen triple helix repeat containing 1 (CTHRC1) was identified as a novel gene expressed in the adventitia and neointima on arterial injury and was found to be overexpressed in several malignant tumors, such as breast cancer and malignant melanoma. However, the expression of Cthrc1 and its role in gastric cancer progression remain unknown. We investigated the expression of the Cthrc1 protein by immunohistochemistry in 30 normal tissues from the control subjects and 166 gastric carcinomas and analyzed its correlation with various clinicopathological features, including patient outcome. Cthrc1 immunoreactivity was overexpressed in gastric carcinoma cases compared with normal tissues (P < .001). High Cthrc1 expression was found in 108 (65.06%) of these 166 carcinomas and was positively correlated with the American Joint Committee on Cancer stage classification, depth of gastric wall invasion, lymph node metastasis, lymphovascular space involvement, and recurrence but not with age, tumor site, and carcinoembryonic antigen level. Patients with high Cthrc1 expression had significantly poorer overall survival and disease-free survival compared with patients with low expression of Cthrc1 (P = .001 and P = .002, respectively). Multivariate analysis showed that high Cthrc1 expression was an independent prognostic factor for both overall survival and disease-free survival of patients with gastric carcinoma (both P = .005). These results showed that high Cthrc1 expression was associated with progression and prognosis of gastric carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Gastric Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Gastric cancer treatment options depend on extent of disease and may include radical surgery, chemotherapy, radiation, and immunotherapy. Get detailed information about the diagnosis, treatment, and prognosis of newly diagnosed and recurrent gastric cancer in this clinician summary.

Soluble E-cadherin is an independent pretherapeutic factor for long-term survival in gastric cancer.

PubMed

Chan, Annie On-On; Chu, Kent-Man; Lam, Shiu-Kum; Wong, Benjamin Chun-Yu; Kwok, Ka-Fai; Law, Simon; Ko, Samuel; Hui, Wai-Mo; Yueng, Yui-Hung; Wong, John

2003-06-15

To evaluate whether pretherapeutic serum soluble E-cadherin is an independent factor predicting long-term survival in gastric cancer. Gastric cancer remains the second leading cause of cancer-related deaths in the world, but a satisfactory tumor marker is currently unavailable for gastric cancer. Soluble E-cadherin has recently been found to have prognostic value in gastric cancer. One hundred sixteen patients with histologically proven gastric adenocarcinoma were included in the trial. Pretherapeutic serum was collected, and soluble E-cadherin was assayed using a commercially available enzyme-linked immunosorbent assay kit. The patients were followed up prospectively at the outpatient clinic. There were 75 men and 41 women, with a mean (+/- SD) age of 66 +/- 14 years. Forty-eight percent of tumors were located in the gastric antrum. The median survival time was 11 months. The mean pretherapeutic value of soluble E-cadherin was 9,159 ng/mL (range, 6,002 to 10,025 ng/mL), and the mean pretherapeutic level of carcinoembryonic antigen was 11 ng/mL (range, 0.3 to 4,895 ng/mL). On multivariate analysis, soluble E-cadherin is an independent factor predicting long-term survival. Ninety percent of patients with a serum level of E-cadherin greater than 10,000 ng/mL had a survival time of less than 3 years (P =.009). Soluble E-cadherin is a potentially valuable pretherapeutic prognostic factor in patients with gastric cancer.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population

PubMed Central

2010-01-01

Background This study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population. Methods We conducted a population-based large-scale case-control study involving 2,213 patients with newly diagnosed gastric cancer, 1,829 patients with newly diagnosed colorectal cancer, and 1,700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. The statistical significance was estimated by logistic regression analysis. Results The MTHFR C677T frequencies of CC, CT, and TT genotypes were 35.2%, 47.5%, and 17.3% among stomach cancer, 34%, 50.5%, and 15.5% in colorectal cancer, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677TT genotype showed a weak opposite association with colorectal cancer compared to the homozygous CC genotype [adjusted age and sex odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.638-0.984, P = 0.035]. Subjects with the MTHFR 677CT showed a significantly reduced risk of gastric cancer compared whose with the 677CC genotype (age- and sex-adjusted OR = 0.810; 95% CI = 0.696-0.942, P = 0.006). We also observed no significant interactions between the MTHFR C677T polymorphism and smoking or drinking in the risk of gastric and colorectal cancer. Conclusions The T allele was found to provide a weak protective association with gastric cancer and colorectal cancer. PMID:20504332

in Mapping of Gastric Cancer Incidence in Iran

PubMed

Asmarian, Naeimehossadat; Jafari-Koshki, Tohid; Soleimani, Ali; Taghi Ayatollahi, Seyyed Mohammad

2016-10-01

Background: In many countries gastric cancer has the highest incidence among the gastrointestinal cancers and is the second most common cancer in Iran. The aim of this study was to identify and map high risk gastric cancer regions at the county-level in Iran. Methods: In this study we analyzed gastric cancer data for Iran in the years 2003-2010. Areato- area Poisson kriging and Besag, York and Mollie (BYM) spatial models were applied to smoothing the standardized incidence ratios of gastric cancer for the 373 counties surveyed in this study. The two methods were compared in term of accuracy and precision in identifying high risk regions. Result: The highest smoothed standardized incidence rate (SIR) according to area-to-area Poisson kriging was in Meshkinshahr county in Ardabil province in north-western Iran (2.4,SD=0.05), while the highest smoothed standardized incidence rate (SIR) according to the BYM model was in Ardabil, the capital of that province (2.9,SD=0.09). Conclusion: Both methods of mapping, ATA Poisson kriging and BYM, showed the gastric cancer incidence rate to be highest in north and north-west Iran. However, area-to-area Poisson kriging was more precise than the BYM model and required less smoothing. According to the results obtained, preventive measures and treatment programs should be focused on particular counties of Iran. Creative Commons Attribution License

Management of gastric cancer in Asia: resource-stratified guidelines.

PubMed

Shen, Lin; Shan, Yan-Shen; Hu, Huang-Ming; Price, Timothy J; Sirohi, Bhawna; Yeh, Kun-Huei; Yang, Yi-Hsin; Sano, Takeshi; Yang, Han-Kwang; Zhang, Xiaotian; Park, Sook Ryun; Fujii, Masashi; Kang, Yoon-Koo; Chen, Li-Tzong

2013-11-01

Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from Asian countries. With a high mortality-to-incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries. Copyright © 2013 Elsevier Ltd. All rights reserved.

Host pathogen interactions in Helicobacter pylori related gastric cancer

PubMed Central

Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

2017-01-01

Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

Host pathogen interactions in Helicobacter pylori related gastric cancer.

PubMed

Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

2017-03-07

Helicobacter pylori ( H. pylori ), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori -related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori -driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.

Interleukin-10 -1082 promoter polymorphism associated with gastric cancer among Asians.

PubMed

Zhou, Yong; Li, Ni; Zhuang, Wen; Liu, Guan-Jian; Wu, Tai-Xiang; Yao, Xun; Du, Liang; Wei, Mao-Ling; Wu, Xiao-Ting

2008-11-01

Studies investigating the association between interleukin-10 (IL-10) -1082 promoter polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarise the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 13 case-control studies, which included 2227 gastric cancer cases and 3538 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [AA odds ratio (OR)=0.92, 95% confidence interval (CI)=0.73, 1.14; AG (OR=1.09, 95% CI=0.87, 1.36); GG (OR=1.03, 95% CI=0.85, 1.25)] between gastric cancer and noncancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly lower frequency of AA (OR=0.71, 95% CI=0.52, 0.97) and higher frequency AG (OR=1.53, 95% CI=1.15, 2.03) than noncancer patients among Asians. When stratifying by the location of gastric cancer, we found that patients with cardia gastric cancer had a significantly lower frequency of AA (OR=0.53, 95% CI=0.34, 0.83) and higher frequency AG (OR=1.50, 95% CI=1.06, 2.11) than those with noncardia gastric cancer among Caucasians. When stratifying by the Lauren's classification of gastric cancer, we observed no statistically significant differences in genotype distribution. This meta-analysis suggests that the IL-10 -1082 promoter polymorphism may be associated with gastric cancer among Asians, and that differences in genotype distribution may be associated with the location of gastric cancer.

Salt taste preference, sodium intake and gastric cancer in China.

PubMed

Zhang, Zhiyong; Zhang, Xiefu

2011-01-01

The risk factors mostly strongly associated with gastric cancer are gastric bacteria Helicobacter pylori and diet. By using a case-control study among residents in China, we examined the association between sodium intake, presence of H,pylori, and gastric cancer risk. A population-based case-control study including 235 cases and 410 controls were used. Potential risk factors of gastric cancer were interview for cases and controls by questionnaire, salt taste preference was measured for all subjects, and IgG antibodies to H,pylori was used for H.pylori infection. Risk measures were calculated using unconditional logistic regression. H.pylori infection and smoking increased the risk of gastric cancer, with the OR(95%CI) of 1.91(1.32-2.79) and 1.47(1.05- 2.05), respectively. Dietary sodium intake independently increased the risk of gastric cancer. Participants with the highest sodium intake(>5g/day) had a high gastric cancer risk [OR(95%CI)= 3.78(1.74-5.44)]. Participants with the salt taste preference at 7.3g/L and ≥ 14.6g/L showed higher risk of gastric cancer [OR(95%) for 7.3g/L and ≥ 14.6g/L were 5.36(2.72-10.97) and 4.75(2.43-8.85), respectively]. A significantly interaction was found between salt taste preference and H.pylori infection (p=0.037). Salt taste preference was significantly correlated with sodium intake (Correlation coefficient=0.46, p< 0.001). Salt taste preference test could be a simple way to evaluate an inherited characteristic of sodium intake, and our study confirms the gastric cancer is associated with sodium intake and H.pylori.

Significance of aquaporins’ expression in the prognosis of gastric cancer

PubMed Central

Thapa, Saroj; Chetry, Mandika; Huang, Kaiyu; Peng, Yangpei; Wang, Jinsheng; Wang, Jiaoni; Zhou, Yingying; Shen, Yigen; Xue, Yangjing; Ji, Kangting

2018-01-01

Gastric carcinoma is one of the most lethal malignancy at present with leading cause of cancer-related deaths worldwide. Aquaporins (AQPs) are a family of small, integral membrane proteins, which have been evidenced to play a crucial role in cell migration and proliferation of different cancer cells including gastric cancers. However, the aberrant expression of specific AQPs and its correlation to detect predictive and prognostic significance in gastric cancer remains elusive. In the present study, we comprehensively explored immunohistochemistry based map of protein expression profiles in normal tissues, cancer and cell lines from publicly available Human Protein Atlas (HPA) database. Moreover, to improve our understanding of general gastric biology and guide to find novel predictive prognostic gastric cancer biomarker, we also retrieved ‘The Kaplan–Meier plotter’ (KM plotter) online database with specific AQPs mRNA to overall survival (OS) in different clinicopathological features. We revealed that ubiquitous expression of AQPs protein can be effective tools to generate gastric cancer biomarker. Furthermore, high level AQP3, AQP9, and AQP11 mRNA expression were correlated with better OS in all gastric patients, whereas AQP0, AQP1, AQP4, AQP5, AQP6, AQP8, and AQP10 mRNA expression were associated with poor OS. With regard to the clinicopathological features including Laurens classification, clinical stage, human epidermal growth factor receptor 2 (HER2) status, and different treatment strategy, we could illustrate significant role of individual AQP mRNA expression in the prognosis of gastric cancer patients. Thus, our results indicated that AQP’s protein and mRNA expression in gastric cancer patients provide effective role to predict prognosis and act as an essential agent to therapeutic strategy. PMID:29678898

Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer

PubMed Central

Sun, Liping; Gong, Yuehua; Chen, Moye; Wang, Zeyang; Yuan, Yuan

2017-01-01

Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival. PMID:28350854

Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer.

PubMed

Lu, Youzhu; Jing, Jingjing; Sun, Liping; Gong, Yuehua; Chen, Moye; Wang, Zeyang; Sun, Mingjun; Yuan, Yuan

2017-01-01

Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival.

Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression.

PubMed

Wu, Lijun; Zhang, Xu; Zhang, Bin; Shi, Hui; Yuan, Xiao; Sun, Yaoxiang; Pan, Zhaoji; Qian, Hui; Xu, Wenrong

2016-09-01

Exosomes are nano-sized membrane vesicles secreted by both normal and cancer cells. Emerging evidence indicates that cancer cells derived exosomes contribute to cancer progression through the modulation of tumor microenvironment. However, the effects of exosomes derived from gastric cancer cells on macrophages are not well understood. In this study, we investigated the biological role of gastric cancer cells derived exosomes in the activation of macrophages. We demonstrated that gastric cancer cells derived exosomes activated macrophages to express increased levels of proinflammatory factors, which in turn promoted tumor cell proliferation and migration. In addition, gastric cancer cells derived exosomes remarkably upregulated the phosphorylation of NF-κB in macrophages. Inhibiting the activation of NF-κB reversed the upregulation of proinflammatory factors in macrophages and blocked their promoting effects on gastric cancer cells. Moreover, we found that gastric cancer cells derived exosomes could also activate macrophages from human peripheral blood monocytes through the activation of NF-κB. In conclusion, our results suggest that gastric cancer cells derived exosomes stimulate the activation of NF-κB pathway in macrophages to promote cancer progression, which provides a potential therapeutic approach for gastric cancer by interfering with the interaction between exosomes and macrophages in tumor microenvironment.

Genomic landscape of gastric cancer: molecular classification and potential targets.

PubMed

Guo, Jiawei; Yu, Weiwei; Su, Hui; Pang, Xiufeng

2017-02-01

Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumorigenesis hinders the development of therapeutic strategies. However, ongoing collaborative sequencing efforts facilitate molecular classification and unveil the genomic landscape of gastric cancer. Several new drivers and tumorigenic pathways in gastric cancer, including chromatin remodeling genes, RhoA-related pathways, TP53 dysregulation, activation of receptor tyrosine kinases, stem cell pathways and abnormal DNA methylation, have been revealed. These newly identified genomic alterations await translation into clinical diagnosis and targeted therapies. Considering that loss-of-function mutations are intractable, synthetic lethality could be employed when discussing feasible therapeutic strategies. Although many challenges remain to be tackled, we are optimistic regarding improvements in the prognosis and treatment of gastric cancer in the near future.

Metastatic gastric cancer from breast carcinoma: A report of 78 cases.

PubMed

Xu, Liang; Liang, Shujing; Yan, Ningning; Zhang, Le; Gu, Hailiang; Fei, Xiaochun; Xu, Yingchun; Zhang, Fengchun

2017-10-01

The metastatic spread of breast carcinoma to the stomach is rare. There are a small number of previous studies that report metastases from the breast to the stomach and these provide limited information regarding this infrequent event. Consequently, the clinicopathological features, clinical outcomes and the optimal treatment for these patients remain to be elucidated. In the present study, 78 cases of gastric metastases from breast cancer, including the current case, were identified from previous studies between 1960 and 2015. The clinicopathological features of primary breast tumors and metastatic gastric lesions, including initial stage, tumor size, hormone receptor status, treatment modalities and overall survival (OS) rate, were analyzed. The patients were all female and the median age at the time of gastric metastasis diagnosis was 59 years old (range, 38-86 years). The majority of the patients initially presented with stage II breast cancer (35.9%) and abdominal pain was the most common symptom of gastric metastases (75.6%). A total of 51/78 patients (65.4%) were identified to have a history of invasive lobular breast carcinoma and the majority of gastric tumors were positive for hormonal receptors and human epidermal growth factor receptor 2 (HER-2) negative (estrogen receptor, 94.0%; progesterone receptor, 68.3%; HER-2, 5.9%). Furthermore, in the univariate analysis, multiple organs involved prior to or at the time of gastric metastases were diagnosed and multiple gastric lesions and peritoneal carcinomatosis were significantly correlated with OS. Additionally, salvage hormonal therapy, but not surgery or chemotherapy, significantly extended OS. However, in the multivariate analysis, metastasis prior to stomach involvement was the only independent indicator of poor OS. In conclusion, physicians must be vigilant when patients with breast cancer history present with gastrointestinal symptoms, despite gastric metastasis from breast cancer being rare. An

Large early gastric cancers treated by endoscopic submucosal dissection with an insulation-tipped diathermic knife.

PubMed

Chang, Chun-Chao; Tiong, Cheng; Fang, Chia-Lang; Pan, Shiann; Liu, Jean-Dean; Lou, Horng-Yuan; Hsieh, Ching-Ruey; Chen, Sheng-Hsuan

2007-03-01

It is difficult to remove a large early gastric cancer (> or = 3 cm) in one-piece resection using conventional endoscopic mucosal resection. We tried to use an insulation-tipped (IT) diathermic knife to dissect these lesions. IT-endoscopic submucosal dissection (ESD) was performed in four aging patients with gastric malignancy. All lesions could be removed in one-piece resection by IT-ESD, although three of them exhibited remarkable fibrosis and ulceration. Three cases experienced curative treatment with IT-ESD after the pathologic evaluation, but it was not curative in one case because the pathology showed angiolymphatic invasion. This patient refused additional surgery in consideration of existing major systemic diseases. At 3 months to 1 year of follow-up, endoscopy showed no evidence of residual cancer. IT-ESD is effective in the treatment of large early gastric cancer and is an alternative treatment for early gastric cancer patients who are at risk for major operation.

Assessment of surgical treatment and postoperative nutrition in gastric cancer patients older than 80 years.

PubMed

Nakanoko, Tomonori; Kakeji, Yoshihiro; Ando, Koji; Nakashima, Yuichiro; Ohgaki, Kippei; Kimura, Yasue; Saeki, Hiroshi; Oki, Eiji; Morita, Masaru; Maehara, Yoshihiko

2015-01-01

A gastrectomy for gastric cancer is sometimes required in patients older than 80 years due to the continuously increasing age of society. However, if a gastrectomy worsens the postoperative quality of life and daily activity in elderly patients because of poor nutrition, the procedure may not always be a useful treatment strategy. Clinicopathological data of patients with gastric cancer who underwent a gastrectomy at our Department between 1998 and 2008 (N=471) were collected and analyzed. The results of treatment for patients older than 80 years (N=41) were analyzed and compared against those of patients younger than 80 years (N=430). Patients older than 80 years had a higher frequency of preoperative co-morbidities than patients younger than 80 years. However, there was no statistical difference in postoperative complications regarding nutrition between the two groups. Older age is not a determinant of poor nutrition following gastrectomy. Gastrectomy for gastric cancer is, therefore, a useful treatment strategy, regardless of ageing. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Upregulation of long non-coding RNA M26317 correlates with tumor progression and poor prognosis in gastric cancer.

PubMed

Li, Li; Wang, Yuan-Yu; Mou, Xiao Zhou; Ye, Zai-Yuan; Zhao, Zhong-Sheng

2018-04-23

To investigate the expression and clinical significance of long non-coding RNA (lnc RNA) in gastric cancer, we applied microarray analysis to obtain expression profiles of protein coding genes and lncRNAs in tumor and paired adjacent non-tumor tissues. We found that 41 lncRNAs were upregulated and 31 lncRNAs were downregulated more than 2-fold in gastric cancer versus noncancerous tissues (ratio>2.0, P<.01). We established a co-expression network of the differentially expressed lncRNAs and targeted coding genes that included 17 lncRNAs and 16 coding genes. As the results of microarray analysis showed that lncRNA M26317 was upregulated in gastric cancer tissues we examined the expression level of M26317 in 103 gastric cancer tissues by RT-PCR and 436 gastric cancer tissues by in situ hybridization. Our data confirmed that M26317 was upregulated in gastric cancer tissues. Moreover, expression of M26317 correlated with patient age, size of tumor, Lauren's classification, depth of invasion, lymph node and distant metastasis, TNM stage and poor prognosis (P<.05), but was not associated with gender, location of tumor, and differentiation (P>.05). M26317 may have an important role in malignant transformation and metastasis of gastric cancer. Copyright © 2018. Published by Elsevier Inc.

Drugs Approved for Stomach (Gastric) Cancer

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for stomach (gastric) cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

A rising trend in the incidence of advanced gastric cancer in young Hispanic men.

PubMed

Merchant, Shaila J; Kim, Joseph; Choi, Audrey H; Sun, Virginia; Chao, Joseph; Nelson, Rebecca

2017-03-01

Although the incidence of gastric cancer has been decreasing, recent reports suggest an increased rate in select populations. We sought to evaluate trends in gastric cancer incidence to identify high-risk populations. Gastric cancer incidence rates from 1992 to 2011 were computed with use of the Surveillance, Epidemiology, and End Results (SEER) registry. We evaluated trends in incidence rates by calculating the annual percent change (APC) across three age groups (20-49 years, 50-64 years, and 65 years or older) and four racial/ethnic groups (Hispanics, non-Hispanic whites, blacks, and Asian/Pacific Islanders). We identified 41,428 patients with gastric cancer. For the entire cohort during the study period, the APC was decreased. When patients were grouped according to sex, the APC was flat or decreased in women regardless of age or race/ethnicity. The APC was also flat or decreased for all men except young Hispanic men (20-49 years), who had an increased APC of nearly 1.6 % (1.55 %, 95 % confidence interval 0.26-2.86 %). Furthermore, young Hispanic men were the only group to have increased incidence of stage IV disease (APC 4.34 %, 95 % confidence interval 2.76-5.94 %) and poorly differentiated tumors (APC 2.08 %, 95 % confidence interval 0.48-3.70 %). The APC of the incidence of gastric cancer in young Hispanic men places it among the top cancers with rising incidence in the USA. This is concomitant with increased incidence of advanced disease at presentation. This major public health concern warrants additional research to determine the cause of the increasing incidence in this group.

Genomic and epigenomic heterogeneity in molecular subtypes of gastric cancer.

PubMed

Lim, Byungho; Kim, Jong-Hwan; Kim, Mirang; Kim, Seon-Young

2016-01-21

Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplified; one way to achieve this is by dividing the disease into subgroups. Toward this effort, recent advances in high-throughput sequencing technology have revealed four molecular subtypes of gastric cancer, which are classified as Epstein-Barr virus-positive, microsatellite instability, genomically stable, and chromosomal instability subtypes. We anticipate that this molecular subtyping will help to extend our knowledge for basic research purposes and will be valuable for clinical use. Here, we review the genomic and epigenomic heterogeneity of the four molecular subtypes of gastric cancer. We also describe a mutational meta-analysis and a reanalysis of DNA methylation that were performed using previously reported gastric cancer datasets.

Mouse models for gastric cancer: Matching models to biological questions

PubMed Central

Poh, Ashleigh R; O'Donoghue, Robert J J

2016-01-01

Abstract Gastric cancer is the third leading cause of cancer‐related mortality worldwide. This is in part due to the asymptomatic nature of the disease, which often results in late‐stage diagnosis, at which point there are limited treatment options. Even when treated successfully, gastric cancer patients have a high risk of tumor recurrence and acquired drug resistance. It is vital to gain a better understanding of the molecular mechanisms underlying gastric cancer pathogenesis to facilitate the design of new‐targeted therapies that may improve patient survival. A number of chemically and genetically engineered mouse models of gastric cancer have provided significant insight into the contribution of genetic and environmental factors to disease onset and progression. This review outlines the strengths and limitations of current mouse models of gastric cancer and their relevance to the pre‐clinical development of new therapeutics. PMID:26809278

A novel approach for the detection of early gastric cancer: fluorescence spectroscopy of gastric juice.

PubMed

Deng, Kai; Zhou, Li Ya; Lin, San Ren; Li, Yuan; Chen, Mo; Geng, Qiu Ming; Li, Yu Wen

2013-06-01

This study aimed to investigate the efficacy of fluorescence spectroscopy of gastric juice for early gastric cancer (EGC) screening. Gastric juice was collected from 101 participants who underwent endoscopy in the Outpatient Endoscopy Center of Peking University Third Hospital. The participants were divided into three groups: the normal mucosa or chronic non-atrophic gastritis (NM-CNAG) group (n = 35), advanced gastric cancer (AGC) group (n = 33) and EGC group (n = 33). Fluorescence spectroscopic analysis was performed in all the gastric juice samples and the maximum fluorescence intensity of the first peak (P1 FI) was measured. The mean fluorescence intensity of P1 FI of gastric juice in AGC (92.1 ± 10.7) and EGC (90.8 ± 12.0) groups was significantly higher than that in the NM-CNAG group (55.7 ± 7.5) (AGC vs NM-CNAG, P = 0.006 and EGC vs NM-CNAG, P = 0.015, respectively). The areas under the receiver operating characteristic curves for the detection of AGC and EGC were 0.681 (95% confidence interval [CI] 0.553-0.810, P = 0.010) and 0.655 (95% CI 0.522-0.787, P = 0.028). With the P1 FI of ≥47.7, the sensitivity, specificity and accuracy for detecting EGC were 69.7%, 57.1% and 63.2%, respectively. The enhancement of P1 FI of gastric juice occurs at the early stage of gastric cancer. Fluorescence spectroscopy of gastric juice may be used as a novel screening tool for the early detection of gastric cancer. © 2013 The Authors. Journal of Digestive Diseases © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

Applications of nanotechnology in gastric cancer: detection and prevention by nutrition.

PubMed

Elingarami, Sauli; Liu, Ming; Fan, Jing; He, Nongyue

2014-01-01

New and emerging technologies, such as nanotechnology, have the potential to advance nutrition science by assisting in the discovery, development, and delivery of several intervention strategies to improve health and reduce the risk and complications of several diseases, including gastric cancer. This article reviews gastric cancer in relation to nutrition, discussing gastric carcinogenesis in-depth in relation to prevention of the disease by nutrition, as well as current detection approaches using nanotechnology. The current status of molecular nutritional biomarkers for gastric cancer is also discussed, as well as future strategies for the tailored management of gastric cancer.

Transgenic and gene knockout mice in gastric cancer research

PubMed Central

Jiang, Yannan; Yu, Yingyan

2017-01-01

Mouse models are useful tool for carcinogenic study. They will greatly enrich the understanding of pathogenesis and molecular mechanisms for gastric cancer. However, only few of mice could develop gastric cancer spontaneously. With the development and improvement of gene transfer technology, investigators created a variety of transgenic and knockout/knockin mouse models of gastric cancer, such as INS-GAS mice and gastrin knockout mice. Combined with helicobacter infection and carcinogens treatment, these transgenic/knockout/knockin mice developed precancerous or cancerous lesions, which are proper for gene function study or experimental therapy. Here we review the progression of genetically engineered mouse models on gastric cancer research, and emphasize the effects of chemical carcinogens or infectious factors on carcinogenesis of genetically modified mouse. We also emphasize the histological examination on mouse stomach. We expect to provide researchers with some inspirations on this field. PMID:27713138

Gastric polyps diagnosed by double-contrast upper gastrointestinal barium X-ray radiography mostly arise from the Helicobacter pylori-negative stomach with low risk of gastric cancer in Japan.

PubMed

Takeuchi, Chihiro; Yamamichi, Nobutake; Shimamoto, Takeshi; Takahashi, Yu; Mitsushima, Toru; Koike, Kazuhiko

2017-03-01

Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is a method broadly used for gastric cancer screening in Japan. Gastric polyp is one of the most frequent findings detected by UGI-XR, but how to handle it remains controversial. Gastric polyps of the 17,264 generally healthy subjects in Japan who underwent UGI-XR or upper gastrointestinal endoscopy (UGI-ES) in 2010 were analyzed. Of the 6,433 UGI-XR examinees (3,405 men and 3,028 women, 47.4 ± 9.0 years old), gastric polyps were detected in 464 men (13.6 %) and 733 women (24.2 %) and were predominantly developed on the non-atrophic gastric mucosa (p < 0.0001). Multiple logistic regression analysis showed that the presence of gastric polyps has significant association with lower value of serum anti-Helicobacter pylori IgG titer, female gender, lighter smoking habit, older age, and normal range of body mass index (≥18.5 and <25), but not with drinking or serum pepsinogen I/II ratio. During the 3-year follow-up, gastric cancer occurred in 7 subjects (0.11 %), but none of them had gastric polyps at the beginning of the follow-up period. Of the 2,722 subjects with gastric polyps among the 10,831 UGI-ES examinees in the same period, 2,446 (89.9 %) had fundic, 267 (9.8 %) had hyperplastic, and 9 (0.3 %) had adenomatous/cancerous polyps. Gastric polyps diagnosed by UGI-XR predominantly arise on the Helicobacter pylori-negative gastric mucosa with a low risk of gastric cancer in Japan. In the prospective observation, none of the UGI-XR examinees with gastric polyps developed gastric cancer for at least 3 years subsequently.

The self-renewal signaling pathways utilized by gastric cancer stem cells.

PubMed

Fu, Ying; Li, Hui; Hao, Xishan

2017-04-01

Gastric cancer is a leading cause of cancer-related mortality worldwide. Cancer stem cells are the source of tumor recurrence and metastasis. Self-renewal is a marker of cancer stem cells and also the basis of long-lasting survival and tumor progression. Although the mechanism of gastric cancer stem cell self-renewal is not clear, there are several signaling pathways and environmental factors known to be involved. This mini review describes recent developments in the self-renewal signaling pathway of gastric cancer stem cell research. Advancements made in this field of research will likely support the development of novel therapeutic strategies for gastric cancer.

Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect.

PubMed

Vogelaar, Ingrid P; Ligtenberg, Marjolijn J L; van der Post, Rachel S; de Voer, Richarda M; Kets, C Marleen; Jansen, Trees J G; Jacobs, Liesbeth; Schreibelt, Gerty; de Vries, I Jolanda M; Netea, Mihai G; Hoogerbrugge, Nicoline

2016-04-01

Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk.

Gastric Cancer Incidence Estimation in a Resource-Limited Nation: Use of Endoscopy Registry Methodology

PubMed Central

Dominguez, Ricardo L.; Crockett, Seth D.; Lund, Jennifer L.; Suazo, Lia P.; Heidt-Davis, Paris; Martin, Christopher; Morgan, Douglas R.

2013-01-01

Purpose Cancer epidemiology is challenging in developing nations, in the absence of reliable pathology-based cancer registries. Clinical experience suggests that the incidence of gastric cancer is high in Honduras, in contrast to the limited available national statistics at the time of study initiation (IARC GLOBOCAN 2002: males 15.2, females 10.8). We estimate the incidence of gastric cancer for Honduras using an endoscopy registry as a complimentary resource. Methods We conducted a retrospective analysis of incident noncardia gastric adenocarcinoma cases in Western Honduras for the period 2000–2009. This region is well circumscribed geopolitically with a single district hospital and established referral patterns, to provide a unique epidemiological niche to facilitate estimation of incidence rates. A prospective, comprehensive database of all endoscopy procedures from this hospital was utilized at the primary data source. The catchment area for gastroenterology services for the at-risk population was validated by calculating the overall endoscopy utilization rates for each municipality in western Honduras. Incident cases of gastric adenocarcinoma were determined by the endoscopic diagnosis. Pathology services are not financed by the Ministry of Health, and histology data was incorporated when available. Population statistics were obtained from the Honduras National Statistics Institute (INE). Age standardized incidence rates (ASIRs) were calculated using world standard population fractions. Results The catchment area for Western Honduras was validated with the municipality threshold of 30 endoscopies per 106 person-years, with inclusion of a total of 40 municipalities. In the Western Honduras catchment area, there were 670 incident cases (439 M, 231 F) of noncardia gastric adenocarcinoma during the study decade 2000–2009. Notably, 67 (10.0%) and 165 (24.6%) of cases were under the ages of 45 and 55, respectively. The case-finding rate was 5.1 endoscopies

Gastric Lgr5+ stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice

PubMed Central

Li, Xiu-Bin; Yang, Guan; Zhu, Liang; Tang, Yu-Ling; Zhang, Chong; Ju, Zhenyu; Yang, Xiao; Teng, Yan

2016-01-01

The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5+ stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5+ stem cells by the inducible Cre-LoxP system and marked mutant Lgr5+ stem cells and their progeny with Cre-reporter Rosa26tdTomato. Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5+ stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5+ chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5+ cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5+ stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression. PMID:27091432

Gastric Lgr5(+) stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice.

PubMed

Li, Xiu-Bin; Yang, Guan; Zhu, Liang; Tang, Yu-Ling; Zhang, Chong; Ju, Zhenyu; Yang, Xiao; Teng, Yan

2016-07-01

The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5(+) stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5(+) stem cells by the inducible Cre-LoxP system and marked mutant Lgr5(+) stem cells and their progeny with Cre-reporter Rosa26(tdTomato). Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5(+) stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5(+) chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5(+) cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5(+) stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression.

Gastric cancer following highly selective vagotomy.

PubMed Central

Houghton, P. W.; Leaper, D. J.

1987-01-01

A case of gastric cancer occurring seven years after a highly selective vagotomy is described. This operation may not be the appropriate choice for the surgical treatment of gastric ulcers and H2 blockers should be used with caution in these patients. PMID:3671228

Gastric tumours in FAP.

PubMed

Walton, Sarah-Jane; Frayling, Ian M; Clark, Susan K; Latchford, Andrew

2017-07-01

Gastric cancer is not a recognised extra-colonic manifestation of FAP, except in countries with a high prevalence of gastric cancer. Data regarding gastric adenomas in FAP are sparse. The aim of this study was to review the clinical characteristics of gastric tumours occurring within an FAP population from the largest European polyposis registry. All patients that developed a gastric adenoma or carcinoma were identified from a prospectively maintained registry database. The primary outcome measure was the occurrence of gastric adenoma or adenocarcinoma. Secondary outcomes included APC mutation, tumour stage, management and survival. Eight patients developed gastric cancer and 21 an adenoma (median age 52 and 44 years, respectively). Regular oesophagogastroduodenoscopy surveillance was performed in 6/8 patients who developed cancer. Half were advanced T3/4 tumours and 6/8 had nodal or metastatic spread at diagnosis. All cancer cases died within a median of 13.5 months from diagnosis. Gastric adenomas were evenly distributed: 11/21 (52%) in the distal and 10/21 (48%) proximal stomach, whereas 5/8 (63%) cancers were located proximally. An association between gastric tumour and desmoid development was observed; 7/8 (88%) cancer and 11/21 (52%) adenoma cases had a personal or family history of desmoid. It would appear from this small, retrospective study that gastric cancer is not a prominent extra-colonic feature of FAP in the Western world. It seems to present at an advanced stage with a poor prognosis. There may be an association between gastric tumour and desmoid occurrence but a large multicentre cohort is necessary to investigate this further.

Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer.

PubMed

Kim, Hye-Young; Cho, Yunhee; Kang, HyeokGu; Yim, Ye-Seal; Kim, Seok-Jun; Song, Jaewhan; Chun, Kyung-Hee

2016-08-02

Wee1 is a member of the Serine/Threonine protein kinase family and is a key regulator of cell cycle progression. It has been known that WEE1 is highly expressed and has oncogenic functions in various cancers, but it is not yet studied in gastric cancers. In this study, we investigated the oncogenic role and therapeutic potency of targeting WEE1 in gastric cancer. At first, higher expression levels of WEE1 with lower survival probability were determined in stage 4 gastric cancer patients or male patients with accompanied lymph node metastasis. To determine the function of WEE1 in gastric cancer cells, we determined that WEE1 ablation decreased the proliferation, migration, and invasion, while overexpression of WEE1 increased these effects in gastric cancer cells. We also validated the clinical application of WEE1 targeting by a small molecule, AZD1775 (MK-1775), which is a WEE1 specific inhibitor undergoing clinical trials. AZD1775 significantly inhibited cell proliferation and induced apoptosis and cell cycle arrest in gastric cancer cells, which was more effective in WEE1 high-expressing gastric cancer cells. Moreover, we performed combination treatments with AZD1775 and anti-cancer agents, 5- fluorouracil or Paclitaxel in gastric cancer cells and in gastric cancer orthotopic-transplanted mice to maximize the therapeutic effect and safety of AZD1775. The combination treatments dramatically inhibited the proliferation of gastric cancer cells and tumor burdens in stomach orthotopic-transplanted mice. Taken together, we propose that WEE1 is over-expressed and could enhance gastric cancer cell proliferation and metastasis. Therefore, we suggest that WEE1 is a potent target for gastric cancer therapy.

Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer

PubMed Central

Kim, Hye-Young; Cho, Yunhee; Kang, HyeokGu; Yim, Ye-Seal; Kim, Seok-Jun; Song, Jaewhan; Chun, Kyung-Hee

2016-01-01

Wee1 is a member of the Serine/Threonine protein kinase family and is a key regulator of cell cycle progression. It has been known that WEE1 is highly expressed and has oncogenic functions in various cancers, but it is not yet studied in gastric cancers. In this study, we investigated the oncogenic role and therapeutic potency of targeting WEE1 in gastric cancer. At first, higher expression levels of WEE1 with lower survival probability were determined in stage 4 gastric cancer patients or male patients with accompanied lymph node metastasis. To determine the function of WEE1 in gastric cancer cells, we determined that WEE1 ablation decreased the proliferation, migration, and invasion, while overexpression of WEE1 increased these effects in gastric cancer cells. We also validated the clinical application of WEE1 targeting by a small molecule, AZD1775 (MK-1775), which is a WEE1 specific inhibitor undergoing clinical trials. AZD1775 significantly inhibited cell proliferation and induced apoptosis and cell cycle arrest in gastric cancer cells, which was more effective in WEE1 high-expressing gastric cancer cells. Moreover, we performed combination treatments with AZD1775 and anti-cancer agents, 5- fluorouracil or Paclitaxel in gastric cancer cells and in gastric cancer orthotopic-transplanted mice to maximize the therapeutic effect and safety of AZD1775. The combination treatments dramatically inhibited the proliferation of gastric cancer cells and tumor burdens in stomach orthotopic-transplanted mice. Taken together, we propose that WEE1 is over-expressed and could enhance gastric cancer cell proliferation and metastasis. Therefore, we suggest that WEE1 is a potent target for gastric cancer therapy. PMID:27363019

Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer

PubMed Central

Kim, Seok-Jun; Wang, Yuan-Guo; Lee, Hyun-Woo; Gu Kang, Hyeok; La, Sun-Hyuk; Ju Choi, Il; Irimura, Tatsuro; Ro, Jae Y.; Bresalier, Robert S.; Chun, Kyung-Hee

2014-01-01

Although elevated expression of neogenin-1 has been detected in human gastric cancer tissue, its role in gastric tumorigenesis remains unclear due to the lack of neogenin-1 studies in cancer. Therefore, we demonstrated here the function and regulatory mechanism of neogenin-1 in gastric cancer. Neogenin-1 ablation decreased proliferation and migration of gastric cancer cells, whereas its over-expression reversed these effects. Xenografted analyses using gastric cancer cells displayed statistically significant inhibition of tumor growth by neogenin-1 depletion. Interestingly, galectin-3 interacted with HSF-1 directly, which facilitated nuclear-localization and binding on neogenin-1 promoter to drive its transcription and gastric cancer cell motility. The galectin-3-increased gastric cancer cell motility was down-regulated by HSF-1 depletion. Moreover, the parallel expression patterns of galectin-3 and neogenin-1, as well as those of HSF-1 and neogenin-1, were detected in the malignant tissues of gastric cancer patients. Taken together, high-expression of neogenin-1 promotes gastric cancer proliferation and motility and its expression is regulated by HSF-1 and galectin-3 interaction. In addition, we propose further studies for neogenin-1 and its associated pathways to provide them as a proper target for gastric cancer therapy. PMID:24930499

Nutrient intake and gastric cancer risk: a case-control study in Spain.

PubMed

Ramón, J M; Serra-Majem, L; Cerdó, C; Oromí, J

1993-12-01

A case-control study of dietary factors and gastric cancer was conducted between September 1986 and March 1989 in the Barcelona metropolitan area, Spain. In all 117 cases with histologically confirmed diagnosis of gastric adenocarcinoma were matched on sex, age and possession of a telephone to 234 population controls. Of the controls 188 (80.3%) were selected by random digit telephone dialing and 46 (19.7%) by neighbourhood of residence. Information about frequency and amount of consumption of 89 alimentary items was gathered by questionnaire, and cases and controls were interviewed in their homes by trained interviewers. The gastric cancer risk decreased in proportion to vitamin C intake. In multivariate analysis adjusting for major covariables, energy and vitamin A intake, the estimated odds ratio (OR) for the upper quartile of vitamin C intake was 0.3 (95% confidence interval [CI]: 0.1-0.8). After adjustment for major covariables, calories and vitamin C intake, vitamin A did not show significant association with the gastric cancer risk. Our findings are consistent with previous case-control studies and with the hypothesis that vitamin C may inhibit the intragastric nitrosation process.

Epstein-Barr virus-associated gastric carcinoma: Evidence of age-dependence among a Mexican population

PubMed Central

Herrera-Goepfert, Roberto; Akiba, Suminori; Koriyama, Chihaya; Ding, Shan; Reyes, Edgardo; Itoh, Tetsuhiko; Minakami, Yoshie; Eizuru, Yoshito

2005-01-01

AIM: To investigate features of Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) among a Mexican population. METHODS: Cases of primary gastric adenocarcinoma were retrieved from the files of the Departments of Pathology at the Instituto Nacional de Cancerología and the Instituto Nacional de la Nutrición in Mexico City. The anatomic site of the gastric neoplasia was identified, and carcinomas were histologically classified as intestinal and diffuse types and subclassified as proposed by the Japanese Research Society for Gastric Cancer. EBV-encoded small non-polyadenylated RNA-1 (EBER-1) in situ hybridization was conducted to determine the presence of EBV in neoplastic cells. RESULTS: We studied 330 consecutive, non-selected, primary gastric carcinomas. Among these, there were 173 male and 157 female patients (male/female ratio 1.1/1). EBER-1 was detected in 24 (7.3%) cases (male/female ratio: 1.2/1). The mean age for the entire group was 58.1 years (range: 20-88 years), whereas the mean age for patients harboring EBER-1-positive gastric carcinomas was 65.3 years (range: 50-84 years). Age and histological type showed statistically significant differences, when EBER-1-positive and -negative gastric carcinomas were compared. EBER-1 was detected in hyperplastic- and dysplastic-gastric mucosa surrounding two EBER-1-negative carcinomas, respectively. CONCLUSION: Among Latin-American countries, Mexico has the lowest frequency of EBVaGC. Indeed, the Mexican population >50 years of age was selectively affected. Ethnic variations are responsible for the epidemiologic behavior of EBVaGC among the worldwide population. PMID:16273633

Randomized trials and quality assurance in gastric cancer surgery.

PubMed

Dikken, Johan L; Cats, Annemieke; Verheij, Marcel; van de Velde, Cornelis J H

2013-03-01

A D2 lymphadenectomy can be considered standard of surgical care for advanced resectable gastric cancer. Currently, several multimodality strategies are used, including postoperative monochemotherapy in Asia, postoperative chemoradiotherapy in the United States, and perioperative chemotherapy in Europe. As the majority of gastric cancer patients are treated outside the framework of clinical trials, quality assurance programs, including referral to high-volume centers and clinical auditing are needed to improve gastric cancer care on a nationwide level. Copyright © 2012 Wiley Periodicals, Inc.

Unemployment risk 2 years and 4 years following gastric cancer diagnosis: a population-based study.

PubMed

Rottenberg, Yakir; Jacobs, Jeremy M; Ratzon, Navah Z; Grinshpun, Albert; Cohen, Miri; Uziely, Beatrice; de Boer, Angela G E M

2017-02-01

The needs of gastric cancer survivors have received limited attention. Returning to work after gastric cancer has not yet been described in a population-based study. We aimed to examine the unemployment risk at 2 and 4 years after gastric cancer. The present historical prospective cohort study included baseline measurements from the Israeli Central Bureau of Statistics 1995 National Census, with follow-up until 2011. A group with gastric cancer and an age-, sex-, and ethnicity-matched control group were sampled from the census population. Binary logistic regression analyses were used to assess odds ratios (ORs) for the study outcomes, controlling for socioeconomic factors, and employment status at 2 years before diagnosis. Data for 152 gastric cancer cases and 464 matched controls were analyzed. Those who died during the study period were excluded. Two years after diagnosis, 53.3 % of gastric cancer survivors and 43.8 % of controls were unemployed (p = 0.04); 4 years after diagnosis, 53.9 % of survivors, and 47.2 % of controls were unemployed (p = 0.15). In the adjusted models, gastric cancer was only associated with unemployment 2 years after diagnosis (OR = 1.47, 95 % confidence interval [CI] = 1.02-2.12). This association weakened and lost significance 4 years after diagnosis (OR = 1.42, 95 % CI = 0.89-2.28). Gastric cancer was not associated with decreased income at 2 (OR = 1.48, 95 % CI = 0.91-1.48) or 4 years (OR = 1.65, 95 % CI = 0.99-2.74) after diagnosis. Gastric cancer survivorship was associated with unemployment 2 years after diagnosis. Longer-term survivors may have the prospect of returning to work. For patients with cancer, returning to work may be an indicator for returning to a normal lifestyle after serious illness. This study highlights the need for early social support in gastric cancer survivors to promote faster recovery.

Modified vs. standard D2 lymphadenectomy in distal subtotal gastrectomy for locally advanced gastric cancer patients under 70 years of age.

PubMed

Zhang, Chun-Dong; Zong, Liang; Ning, Fei-Long; Zeng, Xian-Tao; Dai, Dong-Qiu

2018-01-01

The present study was conducted to investigate the prognosis and survival of patients with locally advanced gastric cancer who underwent distal subtotal gastrectomy with modified D2 (D1+) and D2 lymphadenectomy, under 70 years of age. The five-year overall survival rates of 390 patients were compared between those receiving D1+ and D2 lymphadenectomy. Univariate and multivariate analyses were used to identify factors that correlated with prognosis and lymph node metastasis. Tumor size (P=0.039), pT stage (P=0.011), pN stage (P<0.001), and lymphadenectomy (P=0.004) were identified as independent prognostic factors. Furthermore, tumor size (P=0.022), pT stage (P=0.012), and lymphadenectomy (P=0.028) were proven as independent factors predicting lymph node metastasis. In conclusion, cancers of larger size, higher pT stage, and with D1+ lymphadenectomy had a higher risk of lymph node metastasis. Standard D2 lymphadenectomy removes sufficient lymph nodes to improve staging accuracy and survival. Therefore, D2 lymphanectomy is recommended in distal subtotal gastrectomy for locally advanced gastric cancer, especially for cancers of larger size and higher pT stage.

Robot-assisted surgery for gastric cancer

PubMed Central

Procopiuc, Livia; Tudor, Ştefan; Mănuc, Mircea; Diculescu, Mircea; Vasilescu, Cătălin

2016-01-01

Minimally invasive surgery for gastric cancer is a relatively new research field, with convincing results mostly stemming from Asian countries. The use of the robotic surgery platform, thus far assessed as a safe procedure, which is also easier to learn, sets the background for a wider spread of minimally invasive technique in the treatment of gastric cancer. This review will cover the literature published so far, analyzing the pros and cons of robotic surgery and highlighting the remaining study questions. PMID:26798433

Low junctional adhesion molecule A expression correlates with poor prognosis in gastric cancer.

PubMed

Huang, Jin-Yu; Xu, Ying-Ying; Sun, Zhe; Wang, Zhen-Ning; Zhu, Zhi; Song, Yong-Xi; Luo, Yang; Zhang, Xue; Xu, Hui-Mian

2014-12-01

The aberrant expression of junctional adhesion molecule A (JAM-A), which has a close correlation with the development, progression, metastasis, and prognosis of cancer, has been frequently reported. However, neither JAM-A expression nor its correlation with clinicopathologic variables and patient survival has been defined in gastric cancers. Moreover, little is known about the role of JAM-A in gastric cancer progression. We carried out the present study to investigate the prognostic value of JAM-A expression in gastric cancer patients. Furthermore, the biological roles of JAM-A in gastric cancer progression were also investigated. We determined JAM-A expression in 167 primary gastric cancer tissues and 94 matched adjacent non-tumor tissues by immunohistochemistry. Transwell migration assays and matrigel invasion assays were used to explore the role of JAM-A in gastric cancer cells migration and invasion. CCK-8 assays were used to examine the effect of JAM-A on the proliferation of gastric cancer cells. JAM-A was downregulated in gastric cancer tissues. Low JAM-A expression was significantly associated with tumor size, lymphatic vessel invasion, lymph node metastasis, and TNM stage. Low JAM-A expression was also significantly associated with poor disease-specific survival in gastric cancer patients. Multivariate analysis demonstrated low JAM-A expression as an independent factor predicting poor survival. In addition, JAM-A had the effect on inhibition of gastric cancer cells migration and invasion. However, JAM-A had no significant effects on proliferation of gastric cancer cells. Low JAM-A expression correlates with poor clinical outcome and promotes cell migration and invasion in gastric cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tarnawski, A.; University of California, Irvine, CA 92697; E-mail: andrzej.tarnawski@med.va.gov

Rebamipide accelerates healing of gastric ulcers and gastritis but its actions on gastric cancer are not known. Survivin, an anti-apoptosis protein, is overexpressed in stem, progenitor, and cancer cells. In gastric cancer, increased and sustained survivin expression provides survival advantage and facilitates tumor progression and resistance to anti-cancer drugs. Aurora-B kinase is essential for chromosome alignment and mitosis progression but surprisingly its role in gastric cancer has not been explored. We examined in human gastric cancer AGS cells: (1) survivin expression, (2) localization of survivin and Aurora-B (3) cell proliferation, and (4) effects of specific survivin siRNA and/or rebamipide (freemore » radical scavenging drug) on survivin and Aurora-B expression and cell proliferation. Survivin and Aurora-B are strongly expressed in human AGS gastric cancer cells and co-localize during mitosis. Survivin siRNA significantly reduces AGS cell viability. Rebamipide significantly downregulates in AGS cell survivin expression, its association with Aurora-B and cell proliferation. Rebamipide-induced downregulation of survivin is at the transcription level and does not involve ubiquitin-proteasome pathway.« less

Circular RNA 0000096 affects cell growth and migration in gastric cancer.

PubMed

Li, Peifei; Chen, Huilin; Chen, Shengcan; Mo, Xiaoyan; Li, Tianwen; Xiao, Bingxiu; Yu, Rui; Guo, Junming

2017-02-28

Circular RNAs (circRNAs) are a class of non-coding RNAs broadly expressed in cells of various species. Their role in cancers, especially in gastric cancer, is poorly understood. Circular RNA 0000096 (hsa_circ_0000096) levels in 101 paired gastric cancer tissues and adjacent non-tumorous tissues from patients with gastric cancer were detected by real-time quantitative reverse transcription-polymerase chain reaction. A receiver operating characteristic curve was generated to evaluate the diagnostic value of hsa_circ_0000096. RNA interference was used to manipulate the expression of hsa_circ_0000096. Its biological effects were evaluated by flow cytometry, real-time cell analysis, a wound scratch assay, western blot analysis and xenograft models. Hsa_circ_0000096 was found to be significantly downregulated in gastric cancer tissues and gastric cancer cell lines compared with paired adjacent non-tumorous tissues and normal gastric epithelial cells (P<0.001). Moreover, knockdown of hsa_circ_0000096 significantly inhibited cell proliferation and migration in vitro and in vivo. The results of both immunohistochemical and western blot analyses showed that the protein levels of cyclin D1, cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-2 and MMP-9 were significantly reduced in vitro and in vivo. A gastric cancer xenograft nude mouse model indicated that Ki67 and VEGF were reduced in a dose-dependent manner following knockdown of hsa_circ_0000096. However, the expression of E-cadherin increased. Hsa_circ_0000096 may be used as a potential novel biomarker for gastric cancer. It affects gastric cancer cell growth and migration by regulating cyclin D1, CDK6, MMP-2 and MMP-9.

RISK AND PROTECTIVE FACTORS FOR GASTRIC METAPLASIA AND CANCER: A HOSPITAL-BASED CASE-CONTROL STUDY IN ECUADOR.

PubMed

Salvador, Iván; Mercado, Andrés; Bravo, Gabriela Liliana; Baldeón, Manuel; Fornasini, Marco

2015-09-01

worldwide, stomach cancer is the fifth most frequent cancer, with 952 000 new cases diagnosed in 2012. Ecuador currently holds the 15th place of countries with the highest incidence of stomach cancer for both sexes. the objective of this study was to evaluate risk and protective factors for gastric cancer/metaplasia. a hospital-based case-control study was conducted in Quito, Ecuador. Cases were defined as patients with histological confirmation of gastric cancer (N = 60) or incomplete gastric metaplasia (N = 53). Controls were defined as patients free of gastric cancer or premalignant lesions (N = 144). All participants were personally interviewed using a structured questionnaire to collect data about dietary habits, lifestyle and medical history. risk factors significantly associated to the presence of gastric cancer/metaplasia were the consumption of reheated foods at least 3 times per week (AOR: 4.57; CI: 2.2 - 9.5) and adding salt to more than 50% of foods (AOR: 1.32; CI: 1.04 - 1.67). Protective factors for gastric cancer/metaplasia were the use of non-steroidal anti-inflammatory drugs (AOR: 0.39; CI 0.19 - 0.83), age less than 58 years old (AOR: 0.38; CI: 0.18 - 0.79) and have received treatment for H. Pylori infection (AOR: 0.33; CI: 0.16 - 0.71). this study reports for the first time, the risk and protective factors associated with gastric cancer and metaplasia in Ecuador. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients.

PubMed

Yu, Guoqin; Torres, Javier; Hu, Nan; Medrano-Guzman, Rafael; Herrera-Goepfert, Roberto; Humphrys, Michael S; Wang, Lemin; Wang, Chaoyu; Ding, Ti; Ravel, Jacques; Taylor, Philip R; Abnet, Christian C; Goldstein, Alisa M

2017-01-01

Helicobacter pylori ( Hp ) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.

Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients

PubMed Central

Yu, Guoqin; Torres, Javier; Hu, Nan; Medrano-Guzman, Rafael; Herrera-Goepfert, Roberto; Humphrys, Michael S.; Wang, Lemin; Wang, Chaoyu; Ding, Ti; Ravel, Jacques; Taylor, Philip R.; Abnet, Christian C.; Goldstein, Alisa M.

2017-01-01

Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3–V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications. PMID:28730144

Breast cancer metastasis to the stomach resembling early gastric cancer.

PubMed

Eo, Wan Kyu

2008-12-01

Breast cancer metastases to the stomach are infrequent, with an estimated incidence rate of approximately 0.3%. Gastric metastases usually are derived from lobular rather than from ductal breast cancer. The most frequent type of a breast cancer metastasis as seen on endoscopy to the stomach is linitis plastica; features of a metastatic lesion that resemble early gastric cancer (EGC) are extremely rare. In this report, we present a case of a breast cancer metastasis to the stomach from an infiltrating ductal carcinoma (IDC) of the breast in a 48-year-old woman. The patient had undergone a left modified radical mastectomy with axillary dissection nine years prior. A gastric endoscopy performed for evaluation of nausea and anorexia showed the presence of a slightly elevated mucosal lesion in the cardia, suggestive of a type IIa EGC. A histological examination revealed nests of a carcinoma in the subepithelial lymphatics, and immunohistochemical staining for estrogen receptor was positive. This is an extremely rare case with features of type IIa EGC, but the lesion was finally identified as a cancer metastasis to the cardia of the stomach from an IDC of the breast.

Lymph node involvement in gastric cancer for different tumor sites and T stage: Italian Research Group for Gastric Cancer (IRGGC) experience.

PubMed

Di Leo, Alberto; Marrelli, Daniele; Roviello, Franco; Bernini, Marco; Minicozzi, AnnaMaria; Giacopuzzi, Simone; Pedrazzani, Corrado; Baiocchi, Luca Gian; de Manzoni, Giovanni

2007-09-01

The aim of lymphadenectomy is to clear all the metastatic nodes achieving a complete removal of the tumor; nevertheless, its role in gastric cancer has been very much debated. The frequency of node metastasis in each lymphatic station according to the International Gastric Cancer Association, was studied in 545 patients who underwent D2 or D3 lymphadenectomy from June 1988 to December 2002. Upper third early cancers have shown an involvement of N2 celiac nodes in 25%. In advanced cancers, there was a high frequency of metastasis in the right gastroepiploic (from 10% in T2 to 50% in T4) and in the paraaortic nodes (26% in T2, 32% in T3, 38 % in T4). N3 left paracardial nodes involvement was observed in an important share of middle third tumors (17% in T3, 36% in T4). Splenic hilum nodes metastasis were common in T3 and T4 cancers located in the upper (39%) and middle (17%) stomach. N2 nodal involvement was frequent in lower third advanced cancers. Metastasis in M left paracardial and short gastric nodes were observed in a small percentage of cases. Given the nodal diffusion in our gastric cancer patients, extended lymphadenectomy is still a rationale to obtain radical resection.

Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers

PubMed Central

Garcia-Bloj, Benjamin; Fry, Jacqueline; Wichmann, Ignacio

2015-01-01

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection by Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade. PMID:26379360

Concurrent apatinib and local radiation therapy for advanced gastric cancer

PubMed Central

Zhang, Ming; Deng, Weiye; Cao, Xiaoci; Shi, Xiaoming; Zhao, Huanfen; Duan, Zheping; Lv, Bonan; Liu, Bin

2017-01-01

Abstract Rationale: Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer. Patient concerns and Diagnoses: we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy. Interventions and Outcomes: The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection. Lessons: Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer. PMID:28248891

Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography.

PubMed

Ohata, Hiroshi; Oka, Masashi; Yanaoka, Kimihiko; Shimizu, Yasuhito; Mukoubayashi, Chizu; Mugitani, Kouichi; Iwane, Masataka; Nakamura, Hideya; Tamai, Hideyuki; Arii, Kenji; Nakata, Hiroya; Yoshimura, Noriko; Takeshita, Tetsuya; Miki, Kazumasa; Mohara, Osamu; Ichinose, Masao

2005-10-01

With the aim of developing more efficient gastric cancer screening programs for use in Japan, we studied a new screening program that combines serum pepsinogen (PG) testing and barium digital radiography (DR). A total of 17 647 middle-aged male subjects underwent workplace screening over a 7-year period using a combination of PG testing and DR. This program's effectiveness, as well as other characteristics of the program, was analyzed. Forty-nine cases of gastric cancer were detected (comprising 88% early cancer cases). The detection rate was 0.28%, and the positive predictive value was 0.85%. The PG test detected 63.3% of cases, DR detected 69.4% of cases, and both tests were positive in 32.7% of cancer cases. The two methods were almost equally effective, and were considerably more effective than conventional screening using photofluorography. Each screening method detected a distinct gastric cancer subgroup; the PG test efficiently detected asymptomatic small early cancer with intestinal type histology, while DR was efficient at detecting cancers with depressed or ulcerated morphology and diffuse type histology. The cost for the detection of a single cancer was much less than that for conventional screening. In fact, it is possible to further reduce the cost of detecting a single cancer to a cost comparable to that of surgically resecting a single gastric cancer. Thus, it is probable that a highly efficient gastric cancer screening system can be implemented by combining the two screening methods. Such a screening program would be beneficial in a population at high risk for gastric cancer.

HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9.

PubMed

Chen, Shi-Wei; Zhang, Qing; Xu, Zhi-Feng; Wang, Hai-Ping; Shi, Yi; Xu, Feng; Zhang, Wen-Jian; Wang, Ping; Li, Yong

2016-10-01

Previous studies have demonstrated that the homoebox C6 (HOXC6) gene is highly expressed in gastric cancer tissues and is associated with the depth of tumor invasion, and is associated with poor prognosis of gastric cancer patients expressing HOXC6. The present study investigated the effect and underlying mechanism of HOXC6 on the proliferation and metastasis of gastric cancer cells in vitro. Reverse transcription‑quantitative polymerase chain (PCR) reaction was used to investigate the expression levels of HOXC6 in different gastric cancer cell lines and the effect of different levels of expression on the proliferation of gastric cancer cells was determined by cell growth curve and plate colony formation. The effect of HOXC6 on the anchorage‑independent proliferation of gastric cancer cells was determined by soft agar colony formation assay while the Transwell invasion assay was used to investigate the effect of different levels of HOXC6 expression on the invasive and metastatic abilities of gastric cancer cells. Semi‑quantitative PCR was used to detect the effect of different levels of HOXC6 expression on the expression of matrix metalloproteinase (MMP)2 and MMP9 in gastric cancer cells. Immunoblotting was used to assess MMP9 signaling in the gastric cancer cells. The HOXC6 gene is highly expressed in the majority of the gastric cancer cell lines. Overexpression of HOXC6 promoted gastric cancer cell proliferation and colony formation ability while HOXC6 downregulation inhibited cell proliferation and clone forming ability. HOXC6 overexpression also enhanced the soft agar colony formation ability of gastric cancer cells while HOXC6 downregulation decreased the colony formation ability. Upregulated HOXC6 increased the migration and invasion abilities of gastric cancer cells while interfering with HOXC6 expression inhibited the migration and invasion of the gastric cancer cells. The expression of MMP9 was enhanced with an upregulation of HOXC6 expression

Correlation Between Infection Status of Epstein-Barr Virus and 18F-Fluorodeoxyglucose Uptake in Patients with Advanced Gastric Cancer.

PubMed

Na, Sae Jung; Park, Hye Lim; O, Joo Hyun; Lee, Sung Yong; Song, Kyo Young; Kim, Sung Hoon

2017-01-01

Epstein-Barr virus-associated gastric cancer (EBVaGC) is one of the four molecular subtypes of gastric cancer, as defined by the classification recently proposed by The Cancer Genome Atlas. We evaluated the correlation between EBV positivity and 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake by positron emission tomography/computed tomography (PET/CT) in patients with gastric cancer. We retrospectively enrolled patients with gastric cancer who underwent pretreatment 18 F-FDG PET/CT and subsequent surgical resection, and then were diagnosed with advanced gastric cancer (pathologic stage ≥T2 with any N stage). Maximum standardized uptake values (SUV max ) of gastric cancer were measured by pretreatment 18 F-FDG PET/CT. EBV sequences were detected by in situ hybridization (ISH) techniques. We analyzed the correlation between EBV positivity, clinicopathologic features and metabolic activity of the primary tumor. A total of 205 patients were included and 15 (7.3%) patients were identified as having EBV-positive gastric cancer. Age, gender, tumor location, and histological type showed no significant differences between EBV-positive and negative groups. EBV-positive cancer is significantly more frequent in the higher-metabolic-tumor group than in the lower one (p=0.032). The mean SUV max of gastric cancers showed significant differences between EBV-positive and negative groups (9.9±4.2 vs. 7.0±4.8, p=0.026). The infection status of EBV was significantly related to the 18 F-FDG uptake of primary tumors in patients with advanced gastric cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

PubMed

Jácome, Alexandre Andrade Dos Anjos; Lima, Enaldo Melo de; Kazzi, Ana Izabela; Chaves, Gabriela Freitas; Mendonça, Diego Cavalheiro de; Maciel, Marina Mara; Santos, José Sebastião Dos

2016-04-01

Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

Gene Expression Profiling of Gastric Cancer

PubMed Central

Marimuthu, Arivusudar; Jacob, Harrys K.C.; Jakharia, Aniruddha; Subbannayya, Yashwanth; Keerthikumar, Shivakumar; Kashyap, Manoj Kumar; Goel, Renu; Balakrishnan, Lavanya; Dwivedi, Sutopa; Pathare, Swapnali; Dikshit, Jyoti Bajpai; Maharudraiah, Jagadeesha; Singh, Sujay; Sameer Kumar, Ghantasala S; Vijayakumar, M.; Veerendra Kumar, Kariyanakatte Veeraiah; Premalatha, Chennagiri Shrinivasamurthy; Tata, Pramila; Hariharan, Ramesh; Roa, Juan Carlos; Prasad, T.S.K; Chaerkady, Raghothama; Kumar, Rekha Vijay; Pandey, Akhilesh

2015-01-01

Gastric cancer is the second leading cause of cancer death worldwide, both in men and women. A genomewide gene expression analysis was carried out to identify differentially expressed genes in gastric adenocarcinoma tissues as compared to adjacent normal tissues. We used Agilent’s whole human genome oligonucleotide microarray platform representing ~41,000 genes to carry out gene expression analysis. Two-color microarray analysis was employed to directly compare the expression of genes between tumor and normal tissues. Through this approach, we identified several previously known candidate genes along with a number of novel candidate genes in gastric cancer. Testican-1 (SPOCK1) was one of the novel molecules that was 10-fold upregulated in tumors. Using tissue microarrays, we validated the expression of testican-1 by immunohistochemical staining. It was overexpressed in 56% (160/282) of the cases tested. Pathway analysis led to the identification of several networks in which SPOCK1 was among the topmost networks of interacting genes. By gene enrichment analysis, we identified several genes involved in cell adhesion and cell proliferation to be significantly upregulated while those corresponding to metabolic pathways were significantly downregulated. The differentially expressed genes identified in this study are candidate biomarkers for gastric adenoacarcinoma. PMID:27030788

Current role of minimally invasive approaches in the treatment of early gastric cancer

PubMed Central

El-Sedfy, Abraham; Brar, Savtaj S; Coburn, Natalie G

2014-01-01

Despite declining incidence, gastric cancer remains one of the most common cancers worldwide. Early detection in population-based screening programs has increased the number of cases of early gastric cancer, representing approximately 50% of newly detected gastric cancer cases in Asian countries. Endoscopic mucosal resection and endoscopic submucosal dissection have become the preferred therapeutic techniques in Japan and Korea for the treatment of early gastric cancer patients with a very low risk of lymph node metastasis. Laparoscopic and robotic resections for early gastric cancer, including function-preserving resections, have propagated through advances in technology and surgeon experience. The aim of this paper is to discuss the recent advances in minimally invasive approaches in the treatment of early gastric cancer. PMID:24833843

Interleukin-10 -1082 promoter polymorphism and gastric cancer risk in a Chinese Han population.

PubMed

Zhou, Yong; Hu, Wen; Zhuang, Wen; Wu, Xiaoting

2011-01-01

Studies investigating the association between interleukin-10 (IL-10) -1082 promoter polymorphism and gastric cancer risk report conflicting results. Our recent meta-analysis suggests that the IL-10 -1082 promoter polymorphism may be associated with gastric cancer among Asians. The objective of this study was to investigate the association between IL-10 -1082 promoter polymorphism and gastric cancer risk in Chinese Han patients. We extracted the peripheral blood samples in 150 patients with gastric cancer and 150 controls. PCR-RFLP analysis was performed to detect IL-10 -1082 promoter polymorphism in these patients. Patients with gastric cancer had a significantly lower frequency of AA (OR = 0.45, 95% CI = 0.27, 0.76; P = 0.003) than controls. Patients with cardia gastric cancer had a significantly higher frequency of GG (OR = 2.17, 95% CI = 1.08, 4.38; P = 0.03) than those with noncardia gastric cancer. Patients with advanced gastric cancer had a significantly higher frequency of AA (OR = 5.21, 95% CI = 1.71, 15.87; P = 0.004) than those with early gastric cancer. When stratified by the Lauren's classification, histological differentiation of gastric cancer, no statistically significant results were observed. This study suggests that the IL-10 -1082 promoter polymorphism may be associated with gastric cancer in Chinese Han patients, and that difference in genotype distribution may be associated with the location and stage of gastric cancer.

A case-control study of gastric cancer in Venezuela.

PubMed

Muñoz, N; Plummer, M; Vivas, J; Moreno, V; De Sanjosé, S; Lopez, G; Oliver, W

2001-08-01

A case-control study to evaluate risk factors for gastric cancer was carried out among 292 cases of gastric cancer and 485 controls in a high-risk area of Venezuela. Subjects were interviewed using a structured questionnaire, which elicited information on residential history, socio-economic status, family history of gastric diseases, smoking, drinking and dietary habits. Habitual diet was estimated from a meal-structured food frequency questionnaire on 75 food items. There was a strong inverse association with social class, as measured by education and by indicators of poverty. The results of the dietary analysis suggest that a diet high in starch and low in meat, fish and fresh vegetables increases risk of gastric cancer. A protective effect was observed for frequent consumption of allium vegetables. Inverse associations were found with height, which may reflect nutritional status in childhood, and with refrigerator use in the first two decades of life. Alcohol and tobacco consumption was investigated among males only, since the prevalence of alcohol and tobacco use was very low in females. Alcohol drinkers were at higher risk than non-drinkers and there was a small excess risk for current smokers compared with never smokers. There was some evidence of familial aggregation of gastric cancer. These findings will have important implications in planning preventive strategies for gastric cancer in Venezuela. Copyright 2001 Wiley-Liss, Inc.

Contribution of DNA Repair Xeroderma Pigmentosum Group D Genotype to Gastric Cancer Risk in Taiwan.

PubMed

Ji, Hong-Xue; Chang, Wen-Shin; Tsai, Chia-Wen; Wang, Ju-Yu; Huang, Nai-Kuei; Lee, An-Sheng; Shen, Ming-Yi; Chen, Wei-Yu; Chiang, Yao-Chang; Shih, Tzu-Ching; Hsu, Chin-Mu; Bau, Da-Tian

2015-09-01

It has been proposed that genetic variations of DNA repair genes confer susceptibility to cancer, and the DNA repair gene xeroderma pigmentosum group D (XPD), the caretaker of genome stability, is thought to play a major role in the nucleotide excision repair system. We investigated three genotypes of XPD, at promoter -114 (rs3810366), and codon 312 (rs1799793), 751 (rs13181), and their associated with gastric cancer susceptibility in a Taiwanese population. In the present study, 121 patients with gastric cancer and 363 gender- and age-matched healthy controls were recruited and genotyped for XPD by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology, and the association of XPD genotype with gastric cancer risk was investigated. We found a significant difference in the distribution of A allele-bearing XPD codon 312 genotypes [odds ratio (OR)=1.64, 95% confidence interval (CI)=1.20-2.25, p=0.0019], but not in XPD codon 751 or promoter -114 sites, between the gastric cancer and control groups. Those who had G/A or A/A at XPD codon 312 had a 1.83-fold (95% CI=1.14-2.95, p=0.0159) and 1.87-fold (95% CI=1.04-3.34, p=0.0378) increased risk of gastric cancer compared to those with G/G. The risk for G/A and A/A genotypes had synergistic effects with alcohol drinking (OR=11.27, 95% CI=3.72-34.17, p=0.0001), cigarette smoking (OR=23.20, 95% CI=6.24-86.23, p=0.0001) and Helicobacter pylori infection (OR=5.38, 95% CI=2.76-10.52, p=0.0001) on gastric cancer susceptibility. Our findings suggest that the A allele of XPD codon 312 may contribute to gastric carcinogenesis and may be useful for early detection and prevention of gastric cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Long-Term Low-Dose Aspirin Use Reduces Gastric Cancer Incidence: A Nationwide Cohort Study.

PubMed

Kim, Young-Il; Kim, So Young; Kim, Ji Hyun; Lee, Jun Ho; Kim, Young-Woo; Ryu, Keun Won; Park, Jong-Hyock; Choi, Il Ju

2016-04-01

The aim of this study was to investigate whether aspirin use can reduce the incidence of gastric cancer in patients with hypertension or type 2 diabetes. A total of 200,000 patients with hypertension or type 2 diabetes were randomly selected from the Korean National Health Insurance claim database. Of these, 3,907 patients who used 100 mg of aspirin regularly (regular aspirin users) and 7,808 patients who did not use aspirin regularly (aspirin non-users) were selected at a frequency of 1:2, matched by age, sex, comorbid illnesses (type 2 diabetes and hypertension), and observation periods. The incidence of gastric cancer in this cohort was then assessed during the observation period of 2004 to 2010. In the matched cohort, the incidence rates of gastric cancer were 0.8% (31/3,907) for regular aspirin users and 1.1% (86/7,808) for aspirin non-users, but the cumulative incidence rates were not significantly different between groups (p=0.116, log-rank test). However, in multivariate analysis, regular aspirin users had a reduced risk of gastric cancer (adjusted hazard ratio [aHR], 0.71; 95% confidential interval [CI], 0.47 to 1.08; p=0.107). Duration of aspirin use showed significant association with reduction of gastric cancer risk (aHR for each year of aspirin use, 0.85; 95% CI, 0.73 to 0.99; p=0.044), particularly in patients who used aspirin for more than 3 years (aHR, 0.40; 95% CI, 0.16 to 0.98; p=0.045). Long-term low-dose aspirin use was associated with reduced gastric cancer risk in patients with hypertension or type 2 diabetes.

Trends in gastric cancer mortality and in the prevalence of Helicobacter pylori infection in Portugal.

PubMed

Morais, Samantha; Ferro, Ana; Bastos, Ana; Castro, Clara; Lunet, Nuno; Peleteiro, Bárbara

2016-07-01

Portugal has the highest gastric cancer mortality rates in Western Europe, along with high prevalences of Helicobacter pylori infection. Monitoring their trends is essential to predict the burden of this cancer. We aimed to quantify time trends in gastric cancer mortality in Portugal and in each administrative region, and to compute short-term predictions, as well as to describe the prevalence of H. pylori infection, through a systematic review. Joinpoint analyses were used to identify significant changes in sex-specific trends in gastric cancer age-standardized mortality rates (ASMR) and to estimate annual percent changes (APC). The most recent trends were considered to compute estimates up to 2020 by adjusting Poisson regression models. We searched PubMed and IndexRMP to identify studies carried out in Portugal reporting the prevalence of H. pylori. Gastric cancer mortality has been decreasing in Portugal since 1971 in men (from ASMR=55.3/100 000; APC=-2.4, 95% confidence interval: -2.5 to -2.3) and since 1970 in women (from ASMR=28.0/100 000; APC=-2.8, 95% confidence interval: -2.9 to -2.7), although large regional differences were observed. Predicted ASMR for 2015 and 2020 were 18.8/100 000 and 16.7/100 000 for men and 8.5/100 000 and 7.4/100 000 for women, respectively. The prevalence of H. pylori varied from almost 5% at 0.5-2 years to just over 90% at 70 years or more. No consistent variation was observed since the 1990s. The downward trends in mortality rates are expected to remain in the next decades. The high prevalence of H. pylori infection across age groups and studies from different periods shows a large potential for decrease in the burden of gastric cancer in Portugal.

The endothelial lipase protein is promising urinary biomarker for diagnosis of gastric cancer.

PubMed

Dong, Xueyan; Wang, Guoqing; Zhang, Guoqing; Ni, Zhaohui; Suo, Jian; Cui, Juan; Cui, Ai; Yang, Qing; Xu, Ying; Li, Fan

2013-03-19

Gastric cancer is one of the most common malignant tumors in the world. Finding effective diagnostic biomarkers in urine or serum would represent the most ideal solution to detecting gastric cancer during annual physical examination. This study was to evaluate the potential of endothelial lipase (EL) as a urinary biomarker for diagnosis of gastric cancer. The expression levels of EL was measured using Western blotting and immunohistochemical staining experiments on (tissue, serum, and urine) samples of gastric cancer patients versus healthy people. We also checked the EL levels in the urine samples of other cancer types (lung, colon and rectum cancers) and benign lesions (gastritis and gastric leiomyoma) to check if EL was specific to gastric cancer. We observed a clear separation between the EL expression levels in the urine samples of 90 gastric cancer patients and of 57 healthy volunteers. It was approximately 9.9 fold average decrease of the EL expression levels in the urine samples of gastric cancer compared to the healthy controls (P <0.0001), achieving a 0.967 AUC value for the ROC (receiver operating characteristic) curve, demonstrating it's highly accurate as a diagnostic marker for gastric cancer. Interestingly, the expression levels of EL in tissue and serum samples were not nearly as discriminative as in urine samples (P = 0.90 and P = 0.79). In immunohistochemical experiments, positive expression of the EL protein was found in 67% (8/12) of gastric adjacent noncancerous and in 58% (7/12) of gastric cancer samples. There was no significant statistical in the expression levels of this protein between the gastric cancer and the matching noncancerous tissues (P =0.67). The urinary EL as a highly accurate gastric cancer biomarker that is potentially applicable to the general screening with high sensitivity and specificity. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4527331618757552.

The endothelial lipase protein is promising urinary biomarker for diagnosis of gastric cancer

PubMed Central

2013-01-01

Background Gastric cancer is one of the most common malignant tumors in the world. Finding effective diagnostic biomarkers in urine or serum would represent the most ideal solution to detecting gastric cancer during annual physical examination. This study was to evaluate the potential of endothelial lipase (EL) as a urinary biomarker for diagnosis of gastric cancer. Methods The expression levels of EL was measured using Western blotting and immunohistochemical staining experiments on (tissue, serum, and urine) samples of gastric cancer patients versus healthy people. We also checked the EL levels in the urine samples of other cancer types (lung, colon and rectum cancers) and benign lesions (gastritis and gastric leiomyoma) to check if EL was specific to gastric cancer. Result We observed a clear separation between the EL expression levels in the urine samples of 90 gastric cancer patients and of 57 healthy volunteers. It was approximately 9.9 fold average decrease of the EL expression levels in the urine samples of gastric cancer compared to the healthy controls (P <0.0001), achieving a 0.967 AUC value for the ROC (receiver operating characteristic) curve, demonstrating it’s highly accurate as a diagnostic marker for gastric cancer. Interestingly, the expression levels of EL in tissue and serum samples were not nearly as discriminative as in urine samples (P = 0.90 and P = 0.79). In immunohistochemical experiments, positive expression of the EL protein was found in 67% (8/12) of gastric adjacent noncancerous and in 58% (7/12) of gastric cancer samples. There was no significant statistical in the expression levels of this protein between the gastric cancer and the matching noncancerous tissues (P =0.67). Conclusions The urinary EL as a highly accurate gastric cancer biomarker that is potentially applicable to the general screening with high sensitivity and specificity. Virtual Slides The virtual slide(s) for this article can be found here: http

Stromal-Based Signatures for the Classification of Gastric Cancer.

PubMed

Uhlik, Mark T; Liu, Jiangang; Falcon, Beverly L; Iyer, Seema; Stewart, Julie; Celikkaya, Hilal; O'Mahony, Marguerita; Sevinsky, Christopher; Lowes, Christina; Douglass, Larry; Jeffries, Cynthia; Bodenmiller, Diane; Chintharlapalli, Sudhakar; Fischl, Anthony; Gerald, Damien; Xue, Qi; Lee, Jee-Yun; Santamaria-Pang, Alberto; Al-Kofahi, Yousef; Sui, Yunxia; Desai, Keyur; Doman, Thompson; Aggarwal, Amit; Carter, Julia H; Pytowski, Bronislaw; Jaminet, Shou-Ching; Ginty, Fiona; Nasir, Aejaz; Nagy, Janice A; Dvorak, Harold F; Benjamin, Laura E

2016-05-01

Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, we integrated a mouse model of stromal activation and gastric cancer genomic information to identify gene expression signatures that may inform treatment strategies. We generated a mouse model in which VEGF-A is expressed via adenovirus, enabling a stromal response marked by immune infiltration and angiogenesis at the injection site, and identified distinct stromal gene expression signatures. With these data, we designed multiplexed IHC assays that were applied to human primary gastric tumors and classified each tumor to a dominant stromal phenotype representative of the vascular and immune diversity found in gastric cancer. We also refined the stromal gene signatures and explored their relation to the dominant patient phenotypes identified by recent large-scale studies of gastric cancer genomics (The Cancer Genome Atlas and Asian Cancer Research Group), revealing four distinct stromal phenotypes. Collectively, these findings suggest that a genomics-based systems approach focused on the tumor stroma can be used to discover putative predictive biomarkers of treatment response, especially to antiangiogenesis agents and immunotherapy, thus offering an opportunity to improve patient stratification. Cancer Res; 76(9); 2573-86. ©2016 AACR. ©2016 American Association for Cancer Research.

Ecological study for refrigerator use, salt, vegetable, and fruit intakes, and gastric cancer.

PubMed

Park, Boyoung; Shin, Aesun; Park, Sue K; Ko, Kwang-Pil; Ma, Seung Hyun; Lee, Eun-Ha; Gwack, Jin; Jung, En-Joo; Cho, Lisa Y; Yang, Jae Jeong; Yoo, Keun-Young

2011-11-01

We used an ecological approach to determine the correlation between vegetable, fruit and salt intakes, refrigerator use, and gastric cancer mortality in Korean population. Information on fruit and vegetable intakes per capita from the National Health and Nutrition Survey, death certificate data from the National Statistical office, refrigerator per household data from Korean Statistical Information Service, and salt/sodium intake data from a cross-sectional survey were utilized. Correlation coefficients were calculated between vegetable and fruit intakes, refrigerator per household, and gastric cancer mortality and between salt and sodium intakes, and gastric cancer mortality and incidence in the four areas. With 5, 10, and 15 years lag time, refrigerator usage and fruit intake were negatively associated with gastric cancer mortality (p < 0.01), but vegetable intake was not associated with gastric cancer mortality. When estimates of salt/sodium intake evaluated by 24-h urine collection in four areas of Korea were compared to the gastric cancer mortality and incidence in these regions, positive correlation was shown between salt/sodium intake, and gastric cancer incidence and mortality. Negative associations between refrigerator use, fruit intake, and gastric cancer mortality and positive associations between salt/sodium intake and gastric cancer mortality and incidence were suggested.

Age trend of the male to female sex ratio in surgical gastric cancer patients at a single institution.

PubMed

Yu, Junxiu; He, Yongjun; Guo, Zhen

2014-08-21

In previous reports concerning the association between sex disparity and age, gastric cancer (GC) patients were simply divided into younger and older groups by age. We analyzed the age trend of the male to female sex ratio (MFSR) in GC based on patient sequential age in order to observe the changing process of MFSR with age. One thousand seven hundred fifty-one surgical gastric adenocarcinoma patients aged 26 to 85 years were investigated between January 1996 and December 2010. The patients were grouped by age intervals of 5 years. The Cochran-Armitage trend test was used to determine how the MFSR changed with age. The median age of the 1,751 patients with GC was 60 years (26 to 85 years). There were 1,334 male and 417 female patients (MFSR was 3.20). Cochran-Armitage trend test analysis showed that total MFSR increased significantly with age (Z = 5.964, P < 0.0001). Further studies on age groups of 26 to 60 years and 61 to 85 years were conducted. The trend test showed that MFSR increased significantly with age from 26 to 60 years (Z = 7.433, P < 0.0001). However, MFSR did not increase in ages 61 to 85 years (Z = -0.607, P = 0.544). MFSR in GC presented an increasing trend until 60 years of age. The male GC patients showed an increasing tendency, and female GC patients showed a decreasing tendency with age. This trend reached a plateau phase after 60 years of age.

Results of surgery on 6589 gastric cancer patients and immunochemosurgery as the best treatment of advanced gastric cancer.

PubMed Central

Kim, J P; Kwon, O J; Oh, S T; Yang, H K

1992-01-01

Results of 6589 gastric cancer operations at the Department of Surgery, Seoul National University Hospital, from 1970 to 1990 were reported. About two thirds (76.6%) were advanced gastric cancer (stages III and IV). The 5-year survival rate of operated stage III gastric cancer was only 30.6%, with frequent recurrence. Conversely, cell-mediated immunities of advanced gastric cancer patients were significantly decreased. Therefore, to improve the cure rate and to prevent or delay recurrence, curative surgery with confirmation of free resection margins and systematic lymph node dissection of perigastric vessels were performed and followed by early postoperative immunotherapy and chemotherapy (immunochemosurgery) in stage III patients. To evaluate the effect of immunochemosurgery, two randomized trials were studied in 1976 and 1981. In first trial, 5-fluorouracil, mitomycin C, and cytosine arabinoside for chemotherapy and OK 432 for immunotherapy were used. The 5-year survival rates for surgery alone (n = 64) and immunochemosurgery (n = 73) were 23.4% and 44.6%, respectively, a significant difference. In the second trial, there were three groups: group I, immunochemosurgery (n = 159); group II, surgery and chemotherapy (n = 77); and group III, surgery alone (n = 94). 5-Fluorouracil and mitomycin C for chemotherapy and OK-432 for immunotherapy were administered for 2 years. The 5-year survival rate of group I was 45.3%, significantly higher than the 29.8% of group II and than the 24.4% of group III. The postoperative 1-chloro-2.4-dinitrobenzene test, T-lymphocyte percentage, phytohemagglutinin- and con-A-stimulated lymphoblastogenesis and the antibody-dependent cell-mediated cytotoxicity test showed more favorable values in the immunochemosurgery group. Therefore, immunochemosurgery is the best multimodality treatment for advanced gastric cancer. PMID:1417176