|
1
|
Sharma R. Burden of Stomach Cancer Incidence, Mortality, Disability-Adjusted Life Years, and Risk Factors in 204 Countries, 1990-2019: An Examination of Global Burden of Disease 2019. J Gastrointest Cancer 2024; 55:787-799. [PMID: 38265570 DOI: 10.1007/s12029-023-01005-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2023] [Indexed: 01/25/2024]
Abstract
BACKGROUND Stomach cancer is a global health problem and is one of the leading causes of cancer deaths worldwide. This study investigates the spatial and temporal patterns of stomach cancer burden in 204 countries in the last three decades. DATA AND METHODS The estimates of stomach cancer burden and its risk factors were obtained from the Global Burden of Disease (GBD) 2019 study, covering the years 1990 to 2019, across 204 countries within 21 world regions. GBD employs the cause-of-death ensemble modeling framework to calculate disease-specific mortality estimates. Estimated average percent change (EAPC) of absolute counts (incidence, mortality, and disability-adjusted life years (DALYs)) and age-standardized rates (age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDALR)) was calculated in the regions to illustrate the relative changes between 1990 and 2019. Joinpoint regression was used to analyze global trends of stomach cancer burden in the last three decades. RESULTS Incidence of stomach cancer globally increased from 883,396 cases in 1990 to 1.3 million cases in 2019 and number of deaths due to stomach cancer rose from 788,317 in 1990 to 957,185 in 2019. Between 1990 and 2019, the global ASIR decreased from 22.4 per 100,000 to 15.6 per 100,000, the ASMR decreased from 20.5 per 100,000 to 11.9 per 100,000 and the ASDALR declined from 493.4 per 100,000 to 290.6 per 100,000. Trend analysis using joinpoint regression revealed the slowest rise in incident cases and largest decline in ASIR between 2004 and 2016. In 2019, East Asia had the highest number of incident cases, totaling 626,489, followed by high-income Asia-Pacific (128,168) and South Asia (99,399). The ASIR was the highest in East Asia (30.2/100,000) followed by high-income Asia-Pacific (28.2/100,000) and Andean Latin America (22.4/100,000), while high-income North America had the lowest ASIR at 6.1/100,000. In terms of absolute counts, the top three countries in 2019 were China, India, and Japan together accounting for 61.5% of global incident cases, 58.6% of deaths, and DALYs. Mongolia had the highest ASIR (43.7 per 100,000), followed by Bolivia (34.0 per 100,000) and China (30.6 per 100,000) in 2019, while the lowest ASIR was 3.3 per 100,000 in Malawi. Globally, for both sexes combined, 7.8% of stomach cancer DALYs were associated with a diet high in sodium and 17.2% were linked to smoking. Among males, 24.0% of stomach cancer DALYs were attributable to smoking, compared to only 4.3% in females in 2019. CONCLUSION Significant progress has been made globally in the fight against stomach cancer, with the ASIR decreasing by 30.3% and the ASMR by 41.2% between 1990 and 2019. To further reduce the burden of stomach cancer, it is essential to address factors such as Helicobacter pylori prevalence, obesity, and smoking. Additionally, improvements in early detection, socioeconomic development (including better public sanitation, hygiene, and drinking water), and dietary habits are imperative.
Collapse
Affiliation(s)
- Rajesh Sharma
- Humanities and Social Sciences, National Institute of Technology Kurukshetra, Kurukshetra, Haryana, India.
| |
Collapse
|
|
2
|
López MJ, Carbajal J, Alfaro AL, Saravia LG, Zanabria D, Araujo JM, Quispe L, Zevallos A, Buleje JL, Cho CE, Sarmiento M, Pinto JA, Fajardo W. Characteristics of gastric cancer around the world. Crit Rev Oncol Hematol 2023; 181:103841. [PMID: 36240980 DOI: 10.1016/j.critrevonc.2022.103841] [Citation(s) in RCA: 140] [Impact Index Per Article: 70.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 10/06/2022] [Accepted: 10/07/2022] [Indexed: 11/27/2022] Open
Abstract
Gastric cancer is one of the most important malignancies in the world due to the high burden of disease and lethality. In this work, we compared the main characteristics of gastric cancer between different regions of the world. We reviewed public repositories to retrieve epidemiological, molecular, clinicopathological, and risk factor data. Eastern Asia presents the highest incidence of gastric cancer, followed by eastern and central Europe. Intestinal histology was more frequent in Caucasians, while gastric tumors located in the cardias were less frequent in Africa and Latin America. TP53, LRP1B, and ARID1A are consistently the most frequently altered genes in all population groups. Gastric cancer is most frequent in men. African patients tend to be younger and have a higher proportion of women patients. Different patterns can be observed in the presentation of gastric cancer between different regions of the world. More research is needed in Latin America and Africa since these populations are underrepresented.
Collapse
Affiliation(s)
- María J López
- Facultad de Biología, Universidad Nacional San Luis Gonzaga de Ica, Ica, Peru
| | - Junior Carbajal
- Facultad de Biología, Universidad Nacional San Luis Gonzaga de Ica, Ica, Peru
| | | | - Luis G Saravia
- Departmento de Medicina Interna, Hospital Regional de Ica, Ica, Peru
| | - Daniel Zanabria
- Centro de Investigación Básica y Traslacional, Auna Ideas Foundation, Lima, Peru
| | - Jhajaira M Araujo
- Escuela de Medicina, Universidad Privada San Juan Bautista, Lima, Peru
| | - Lidia Quispe
- Departmento of Patología, Hospital Regional de Ica, Ica, Peru
| | | | - José L Buleje
- Escuela de Medicina-Filial Ica, Universidad Privada San Juan Bautista, Ica, Peru
| | | | - Marisol Sarmiento
- Escuela de Medicina-Filial Ica, Universidad Privada San Juan Bautista, Ica, Peru
| | - Joseph A Pinto
- Escuela de Medicina-Filial Ica, Universidad Privada San Juan Bautista, Ica, Peru.
| | - Williams Fajardo
- Escuela de Medicina, Universidad Privada San Juan Bautista, Lima, Peru
| |
Collapse
|
|
3
|
Xu W, Zhao D, Huang X, Zhang M, Zhu W, Xu C. Significance of monocyte infiltration in patients with gastric cancer: A combined study based on single cell sequencing and TCGA. Front Oncol 2022; 12:1001307. [PMID: 36479092 PMCID: PMC9720400 DOI: 10.3389/fonc.2022.1001307] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 10/28/2022] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Gastric cancer is still one of the most lethal tumor diseases in the world. Despite some improvements, the prognosis of patients with gastric cancer is still not accurately predicted. METHODS Based on single cell sequencing data, we conducted a detailed analysis of gastric cancer patients and normal tissues to determine the role of monocytes in the progression of gastric cancer. WCGA facilitated our search for Grade-related genes in TCGA. Then, according to the marker genes and cell differentiation genes of monocytes, we determined the cancer-promoting genes of monocytes. Based on LASSO regression, we established a prognostic model using TCGA database. The accuracy of the model was verified by PCA, ROC curve, survival analysis and prognostic analysis. Finally, we evaluated the significance of the model in clinical diagnosis and treatment by observing drug sensitivity, immune microenvironment and immune checkpoint expression in patients with different risk groups. RESULTS Monocytes were poorly differentiated in tumor microenvironment. It mainly played a role in promoting cancer in two ways. One was to promote tumor progression indirectly by interacting with other tumor stromal cells. The other was to directly connect with tumor cells through the MIF and TNF pathway to play a tumor-promoting role. The former was more important in these two ways. A total of 292 monocyte tumor-promoting genes were obtained, and 12 genes were finally included in the construction of the prognosis model. A variety of validation methods showed that our model had an accurate prediction ability. Drug sensitivity analysis could provide guidance for clinical medication of patients. The results of immune microenvironment and immune checkpoint also indicated the reasons for poor prognosis of high-risk patients. CONCLUSION In conclusion, we provided a 12-gene risk score formula and nomogram for gastric cancer patients to assist clinical drug therapy and prognosis prediction. This model had good accuracy and clinical significance.
Collapse
Affiliation(s)
- Wei Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Dongxu Zhao
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Xiaowei Huang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Man Zhang
- Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Wenxin Zhu
- Department of Gastroenterology, Kunshan Third People’s Hospital, Suzhou, Jiangsu, China
| | - Chunfang Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| |
Collapse
|
|
4
|
Stillman MD, Yoon SS. Open and minimally invasive gastrectomy in Eastern and Western patient populations: A review of the literature and reasons for differences in outcomes. J Surg Oncol 2022; 126:279-291. [PMID: 35416303 PMCID: PMC9276624 DOI: 10.1002/jso.26887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 03/27/2022] [Indexed: 11/08/2022]
Abstract
Randomized trials in the East have established minimally invasive gastrectomy as possibly superior for short-term outcomes and noninferior for long-term survival. Smaller randomized studies from Western countries have supported these findings. However, there are marked disparities in morbidity, mortality, and overall survival noted between Eastern and Western studies. In this article, we review the literature comparing open and minimally invasive gastrectomy in the East and West, and describe the possible reasons for differences in outcomes.
Collapse
Affiliation(s)
- Mason D Stillman
- Division of Surgical Oncology, Department of Surgery, Columbia University Irving Medical Center, New York, New York, USA
| | - Sam S Yoon
- Division of Surgical Oncology, Department of Surgery, Columbia University Irving Medical Center, New York, New York, USA
| |
Collapse
|
|
5
|
Manabe N, Matsueda K, Haruma K. Epidemiological Review of Gastroesophageal Junction Adenocarcinoma in Asian Countries. Digestion 2021; 103:29-36. [PMID: 34718236 DOI: 10.1159/000519602] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 09/13/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Similar trends in the prevalence of gastroesophageal reflux disease (GERD), obesity, and Helicobacter pylori infection have been observed in Asian and Western countries despite their time differences. However, it is unclear whether the prevalence of gastroesophageal junction adenocarcinomas in Asian countries is increasing. In this review, we discuss the epidemiological trends of gastroesophageal junction adenocarcinoma in Asian countries. SUMMARY The prevalence of GERD is increasing in Asian countries, but most cases are considered mild. Obesity is a serious problem worldwide, but it is considered less serious in Asia than in Western countries. In Asian countries where gastric cancer is common, both cardiac and noncardiac cancers are associated with high rates of H. pylori infection, which is considered a carcinogenic risk factor for both sites of cancer. The widespread use of H. pylori eradication therapy for chronic gastritis in several Asian countries has not directly led to an increased prevalence of esophageal adenocarcinoma. One of the originating sites of junctional adenocarcinoma in most Asian countries is Barrett's esophagus, with short-segment Barrett's esophagus having much lower carcinogenicity than long-segment Barrett's esophagus. Key Messages: Considering the future trends of several risk factors for gastroesophageal junction adenocarcinoma in Asian countries, it is likely that the incidence of gastroesophageal junction adenocarcinoma will gradually increase, but not at a rate that exceeds that of squamous cell carcinoma, as in Western countries.
Collapse
Affiliation(s)
- Noriaki Manabe
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Okayama, Japan
| | - Kazuhiro Matsueda
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School, Okayama, Japan
| |
Collapse
|
|
6
|
Huang Q, Read M, Gold JS, Zou XP. Unraveling the identity of gastric cardiac cancer. J Dig Dis 2020; 21:674-686. [PMID: 32975049 DOI: 10.1111/1751-2980.12945] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 08/11/2020] [Accepted: 09/21/2020] [Indexed: 12/11/2022]
Abstract
The classification of gastric cardiac carcinoma (GCC) is controversial. It is currently grouped with esophageal adenocarcinoma (EAC) as an adenocarcinoma of the gastroesophageal junction (GEJ). Recently, diagnostic criteria for adenocarcinoma in the GEJ were established and GCC was separated from EAC. We viewed published evidence to clarify the GCC entity for better patient management. GCC arises in the cardiac mucosa located from 3 cm below and 2 cm above the GEJ line. Compared with EAC, GCC is more like gastric cancer and affects a higher proportion of female patients, younger patients, those with a lower propensity for reflux disease, a wider histopathologic spectrum, and more complex genomic profiles. Although GCC pathogenesis mechanisms remain unknown, the two-etiology proposal is appealing: in high-risk regions, the Correa pathway with Helicobacter pylori infection, chronic inflammation, low acid and intestinal metaplasia, dysplasia and carcinoma may apply, while in low-risk regions the sequence from reflux toxin-induced mucosal injury and high acid, to intestinal metaplasia, dysplasia and carcinoma may occur. In early GCC a minimal risk of nodal metastasis argues for a role of endoscopic therapy, whereas in advanced GCC, gastric cancer staging rules and treatment strategy appear to be more appropriate than the esophageal cancer staging scheme and therapy for better prognosis stratification and treatment. In this brief review we share recent insights into the epidemiology, histopathology and genetics of GCC and hope that this will stimulate further investigations in order to improve the clinical management of patients with GCC.
Collapse
Affiliation(s)
- Qin Huang
- Department of Pathology, Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China.,Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System, Harvard Medical School/Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Matthew Read
- Department of Surgery, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Jason S Gold
- Department of Surgery, Veterans Affairs Boston Healthcare System, Harvard Medical School/Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Xiao Ping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China
| |
Collapse
|
|
7
|
Bharucha PP, Chiu KE, François FM, Scott JL, Khorjekar GR, Tirada NP. Genetic Testing and Screening Recommendations for Patients with Hereditary Breast Cancer. Radiographics 2020; 40:913-936. [PMID: 32469631 DOI: 10.1148/rg.2020190181] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Professionals who specialize in breast imaging may be the first to initiate the conversation about genetic counseling with patients who have a diagnosis of premenopausal breast cancer or a strong family history of breast and ovarian cancer. Commercial genetic testing panels have gained popularity and have become more affordable in recent years. Therefore, it is imperative for radiologists to be able to provide counseling and to identify those patients who should be referred for genetic testing. The authors review the process of genetic counseling and the associated screening recommendations for patients at high and moderate risk. Ultimately, genetic test results enable appropriate patient-specific screening, which allows improvement of overall survival by early detection and timely treatment. The authors discuss pretest counseling, which involves the use of various breast cancer risk assessment tools such as the Gail and Tyrer-Cuzick models. The most common high- and moderate-risk gene mutations associated with breast cancer are also reviewed. In addition to BRCA1 and BRCA2, several high-risk genes, including TP53, PTEN, CDH1, and STK11, are discussed. Moderate-risk genes include ATM, CHEK2, and PALB2. The imaging appearances of breast cancer typically associated with each gene mutation, as well as the other associated cancers, are described. ©RSNA, 2020 See discussion on this article by Butler (pp 937-940).
Collapse
Affiliation(s)
- Puja P Bharucha
- From the Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 22 S Greene St, Baltimore, MD 21201
| | - Kellie E Chiu
- From the Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 22 S Greene St, Baltimore, MD 21201
| | - Fabienne M François
- From the Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 22 S Greene St, Baltimore, MD 21201
| | - Jessica L Scott
- From the Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 22 S Greene St, Baltimore, MD 21201
| | - Gauri R Khorjekar
- From the Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 22 S Greene St, Baltimore, MD 21201
| | - Nikki P Tirada
- From the Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 22 S Greene St, Baltimore, MD 21201
| |
Collapse
|
|
8
|
Liu AQ, Vogtmann E, Shao DT, Abnet CC, Dou HY, Qin Y, Su Z, Wei WQ, Chen W. A Comparison of Biopsy and Mucosal Swab Specimens for Examining the Microbiota of Upper Gastrointestinal Carcinoma. Cancer Epidemiol Biomarkers Prev 2019; 28:2030-2037. [PMID: 31519703 PMCID: PMC7294753 DOI: 10.1158/1055-9965.epi-18-1210] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 04/11/2019] [Accepted: 09/10/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND There is currently no optimal sampling method for upper gastrointestinal (UGI) tract microbiota. We compared biopsies and mucosal swab specimens for microbial sampling from patients with UGI carcinoma. METHODS A total of 67 patients with esophageal squamous cell carcinoma (ESCC) and 36 patients with gastric cardia adenocarcinoma (GCA) were recruited in the Linxian Cancer Hospital (Henan, China). Sterile biopsies and swabs were used to collect paired samples from the resection specimens from carcinoma and adjacent normal tissue. Data from 16S rRNA gene sequencing were processed using QIIME2 to evaluate differences in alpha and beta diversity and taxonomic relative abundances between specimen types. RESULTS Alpha diversity was not significantly different between swab specimens and biopsies, both for ESCC and GCA. Paired specimens were correlated for both sample types from ESCC (ρ > 0.6, P < 0.001) but not GCA (ρ < 0.4, P > 0.05). For beta diversity, distinct clustering by sampling method was not observed for adjacent normal or tumor tissue from ESCC or GCA. There was a high correlation for weighted UniFrac and Bray-Curtis distance only in ESCC paired specimens (ρ > 0.6, P = 0.001). The 10 dominant bacterial genera were similar between swab and biopsy specimens. However, higher levels of Veillonella (P = 0.0002) and Streptococcus (P = 0.0002) were detected in ESCC adjacent normal and GCA carcinoma swabs, respectively, compared with the biopsies. CONCLUSIONS Mucosal swab specimens and biopsies could yield similar microbial profiles from ESCC but not GCA. Both can be used to characterize UGI microbiota; one sampling method should be selected for future studies. IMPACT This study provides insight for planning microbiota collections from the UGI tract.
Collapse
Affiliation(s)
- An-Qi Liu
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Emily Vogtmann
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland
| | - Dan-Tong Shao
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Christian C Abnet
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland
| | - Hao-Yu Dou
- Promegene Translational Research Institute, Shenzhen, China
| | - Yu Qin
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Su
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen-Qiang Wei
- Cancer Registration Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Chen
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| |
Collapse
|
|
9
|
Gastric Cancer in the Era of Immune Checkpoint Blockade. JOURNAL OF ONCOLOGY 2019; 2019:1079710. [PMID: 31662748 PMCID: PMC6778883 DOI: 10.1155/2019/1079710] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Accepted: 08/22/2019] [Indexed: 12/24/2022]
Abstract
Gastric cancer (GC) is one of the most important malignancies worldwide because of its high incidence and mortality. The very low survival rates are mainly related to late diagnosis and limited treatment options. GC is the final clinical outcome of a stepwise process that starts with a chronic and sustained inflammatory reaction mounted in response to Helicobacter pylori infection. The bacterium modulates innate and adaptive immunity presumably as part of the strategies to survive, which favors the creation of an immunosuppressive microenvironment that ultimately facilitates GC progression. T-cell exhaustion, which is characterized by elevated expression of immune checkpoint (IC) proteins, is one of the most salient manifestations of immunosuppressive microenvironments. It has been consistently demonstrated that the tumor-immune microenvironment(TIME)‐exhausted phenotype can be reverted by blocking ICs with monoclonal antibodies. Although these therapies are associated with long-lasting response rates, only a subset of patients derive clinical benefit, which varies according to tumor site. The search for biomarkers to predict the response to IC inhibition is a matter of intense investigation as this may contribute to maximize disease control, reduce side effects, and minimize cost. The approval of pembrolizumab for its use in GC has rocketed immuno-oncology research in this cancer type. In this review, we summarize the current knowledge centered around the immune contexture and recent findings in connection with IC inhibition in GC.
Collapse
|
|
10
|
Liu B, Chen H, Zhang W, Zhang G. A novel technique for removing large gastric subepithelial tumors with ESD method in the subcardia region. Oncol Lett 2019; 18:5277-5282. [PMID: 31612037 PMCID: PMC6781672 DOI: 10.3892/ol.2019.10894] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
Previously, patients with tumors larger than 4 cm in sub-cardia region usually received open gastrectomy. Due to its anatomic features, the cardia is often considered as a contraindicated area for endoscopic resection. Herein, we report a novel technique of endoscopic submucosal dissection (ESD) which facilitates the removal of gastric subepithelial tumors (SMTs) larger than 4 cm in the subcardia and fundus region. This is a retrospective case series of patients with SMTs larger than 4 cm in the subcardia and fundus regions who received the novel procedure of ESD between October 2015 and October 2016. The novel procedure of ESD involved a median linear incision of the mucosa being made in the central area of the tumor, followed by the submucosal dissection. The residual defect was finally closed using titanium endoclips. The endoscopical outcomes, histopathological findings as well as other complications were assessed. Eight patients fulfilled the entry criteria. The mean lesion size was 45.6±7.5 mm (range: 40.0-65.0 mm), and the mean operating time was 83±13 min (range: 60-100 min). The en bloc resection rate was 100%. Although perforations occurred in 5 out of 8 patients, they were successfully closed with endoclips. The median length of inpatient hospital stay was 6 days (range: 5-8 days). No patients needed further gastrectomy. The median follow-up was 36 months and none of the patients developed local recurrence or distant metastasis. The advanced procedure of ESD is feasible and safe for tumors more than 4 cm in the subcardia region. It could be applied as a novel technique for treating patient without surgical interventions.
Collapse
Affiliation(s)
- Bingtuan Liu
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.,The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.,Department of Gastroenterology, Jiangsu Jiangyin People's Hospital, Wuxi, Jiangsu 214400, P.R. China
| | - Han Chen
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Weifeng Zhang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.,The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Guoxin Zhang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| |
Collapse
|
|
11
|
Wang SM, Roth MJ, Murphy GA, Dawsey SM, Fan JH, Taylor PR, Qiao YL, Abnet CC. Serologic Profile of Antiparietal Cell Antibodies, Pepsinogens, and H. pylori and Risk of Upper Gastrointestinal Cancer: A Nested Case-Control Study in China. Cancer Epidemiol Biomarkers Prev 2019; 28:2022-2029. [PMID: 31501152 DOI: 10.1158/1055-9965.epi-19-0512] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 06/26/2019] [Accepted: 09/03/2019] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Autoimmune gastritis is understudied and possibly associated with gastric noncardia adenocarcinoma (GNCA) and esophageal squamous cell carcinoma (ESCC) in Western populations when it presents as pernicious anemia. METHODS A nested case-control study within a Chinese cohort included 100 ESCC, 200 gastric cardia adenocarcinoma (GCA), and 200 GNCA cases diagnosed between 1986 and 2001 and 400 controls. Serostatus of antiparietal cell antibodies (APCA), Helicobacter pylori antibodies, and pepsinogens were measured using commercial kits and serum collected at baseline. We used logistic regression to calculate odds ratios (OR) and 95% confidence interval (CI) for associations between serologic biomarkers and cancer risk adjusted for numerous potential confounders. RESULTS There was an average interval of 8 years between baseline blood draw and cancer diagnosis. The baseline prevalence of APCA seropositivity was 10.0% and 14.5% in subjects who developed GCA and GNCA, respectively. APCA seropositivity was inversely associated with later development of GCA (OR = 0.42; 95% CI, 0.24-0.75), but not significantly associated with later development of GNCA (OR = 0.82; 95% CI, 0.50-1.36) or ESCC (OR = 1.05; 95% CI, 0.58-1.88). APCA seropositivity was significantly associated with low pepsinogen I/II ratios (OR = 3.69; 95% CI, 1.66-8.21), and individuals with low pepsinogen I/II ratios who were seronegative for APCA had the highest risk of both GCA and GNCA. CONCLUSIONS APCA seropositivity measured years prior to diagnosis was associated with prevalent atrophic gastritis but inversely associated with incident GCA in this Chinese population. IMPACT APCA may contribute to a growing list of serologic markers that can improve risk stratification for gastric cancer.
Collapse
Affiliation(s)
- Shao-Ming Wang
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland
| | - Mark J Roth
- Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Gwen A Murphy
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland
| | - Sanford M Dawsey
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland
| | - Jin-Hu Fan
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Philip R Taylor
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland
| | - You-Lin Qiao
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Christian C Abnet
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
| |
Collapse
|
|
12
|
Guo W, Lv P, Liu S, Xu F, Guo Y, Shen S, Liang J, Kuang G, Dong Z. Aberrant methylation-mediated downregulation of long noncoding RNA C5orf66-AS1 promotes the development of gastric cardia adenocarcinoma. Mol Carcinog 2018; 57:854-865. [PMID: 29566283 DOI: 10.1002/mc.22806] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2017] [Revised: 02/28/2018] [Accepted: 03/20/2018] [Indexed: 02/01/2023]
Abstract
As a long non-coding RNA, C5orf66-AS1 is located at 5q31.1. Downregulation and aberrant hypermethylation of C5orf66-AS1 have been detected in a limited several tumors. However, the biological role and distribution of methylated CpG sites of C5orf66-AS1 in gastric cardia adenocarcinoma (GCA) development and prognosis are poorly clarified. The present study was to investigate the expression status and function of C5orf66-AS1 in GCA, and to detect the distribution of methylated CpG sites within the three CpG islands of the promoter and gene body of C5orf66-AS1, further to clarify its prognostic value in GCA patients. C5orf66-AS1 was significantly downregulated in GCA tissues and cell lines, and the expression level was associated with TNM stage, pathological differentiation, lymph node metastasis, and distant metastasis or recurrence. The expression level of C5orf66-AS1 was significantly increased in cancer cells after treated with 5-Aza-dC. Further methylation analysis demonstrated that the aberrant hypermethylation of the regions around the transcription start site of C5orf66-AS1 was more tumor specific and was associated with its expression. Moreover, Sp1 may upregulate C5orf66-AS1 expression and CpG sites hypermethylation within the binding sites may abrogate Sp1 binding. In addition, C5orf66-AS1 inhibited gastric cancer cell proliferation and invasion, and the dysregulation and hypermethylation of the regions around the transcription start site of C5orf66-AS1 were associated with poorer GCA patients' survival. These findings suggest that aberrant hypermethylation-mediated downregulation of C5orf66-AS1 may play important roles in GCA tumorigenesis and C5orf66-AS1 may serve as a potential prognostic marker in predicting GCA patients' survival.
Collapse
Affiliation(s)
- Wei Guo
- Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Ping Lv
- Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Shengnan Liu
- Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Fenglou Xu
- Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Yanli Guo
- Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Supeng Shen
- Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Jia Liang
- Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Gang Kuang
- Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Zhiming Dong
- Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| |
Collapse
|
|
13
|
Khatoon J, Rai RP, Prasad KN. Role of Helicobacter pylori in gastric cancer: Updates. World J Gastrointest Oncol 2016; 8:147-158. [PMID: 26909129 PMCID: PMC4753165 DOI: 10.4251/wjgo.v8.i2.147] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 07/14/2015] [Accepted: 12/15/2015] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is highly prevalent in human, affecting nearly half of the world’s population; however, infection remains asymptomatic in majority of population. During its co-existence with humans, H. pylori has evolved various strategies to maintain a mild gastritis and limit the immune response of host. On the other side, presence of H. pylori is also associated with increased risk for the development of various gastric pathologies including gastric cancer (GC). A complex combination of host genetics, environmental agents, and bacterial virulence factors are considered to determine the susceptibility as well as the severity of outcome in a subset of individuals. GC is one of the most common cancers and considered as the third most common cause of cancer related death worldwide. Many studies had proved H. pylori as an important risk factor in the development of non-cardia GC. Although both H. pylori infection and GC are showing decreasing trends in the developed world, they still remain a major threat to human population in the developing countries. The current review attempts to highlight recent progress in the field of research on H. pylori induced GC and aims to provide brief insight into H. pylori pathogenesis, the role of major virulence factors of H. pylori that modulates the host environment and transform the normal gastric epithelium to neoplastic one. This review also emphasizes on the mechanistic understanding of how colonization and various virulence attributes of H. pylori as well as the host innate and adaptive immune responses modulate the diverse signaling pathways that leads to different disease outcomes including GC.
Collapse
|
|
14
|
Shakeri R, Malekzadeh R, Nasrollahzadeh D, Pawlita M, Murphy G, Islami F, Sotoudeh M, Michel A, Etemadi A, Waterboer T, Poustchi H, Brennan P, Boffetta P, Dawsey SM, Kamangar F, Abnet CC. Multiplex H. pylori Serology and Risk of Gastric Cardia and Noncardia Adenocarcinomas. Cancer Res 2015; 75:4876-4883. [PMID: 26383162 PMCID: PMC4792189 DOI: 10.1158/0008-5472.can-15-0556] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 08/09/2015] [Indexed: 02/06/2023]
Abstract
The reported associations with gastric adenocarcinoma and seropositivity to different Helicobacter pylori antigens using multiplex serology have not been consistent across studies. We aimed to investigate the association between 15 different multiplex serology antigens and the risk of gastric cardia (GCA) and gastric noncardia (GNCA) adenocarcinomas in northeastern Iran, a population with high rates of gastric adenocarcinoma. We included 272 cases of gastric adenocarcinoma (142 GCA, 103 GNCA, and 27 unspecified) and 524 controls who were individually matched to cases for age, sex, and place of residence in a population-based case-control study. Seropositivity to H. pylori was assessed using both multiplex serology and H. pylori IgG ELISA. Ninety-five percent of controls were seropositive to H. pylori. Of the 15 antibodies in the multiplex assay, 11 showed no significant association with gastric adenocarcinomas. CagA and VacA were associated with a significantly increased risk of all gastric adenocarcinoma and GNCA in multivariate models. Surprisingly, GroEL and NapA were significantly associated with a reduced risk of these tumors. Only CagA antigen was associated with significantly elevated risk of GCA. We found no associations between H. pylori seropositivity overall either by whole-cell ELISA test or multiplex serology, likely due to the high prevalence of seropositivity. Individual antigen testing showed that CagA positivity was associated with increased risk of both noncardia and cardia adenocarcinoma, which is similar to some other Asian populations, whereas two antigens were associated with lower risk of gastric cancer. This latter result was unexpected and should be retested in other populations.
Collapse
Affiliation(s)
- Ramin Shakeri
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Dariush Nasrollahzadeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | | | - Gwen Murphy
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Farhad Islami
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. American Cancer Society, Atlanta
| | - Masoud Sotoudeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Arash Etemadi
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | | | - Hossein Poustchi
- Digestive Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Paul Brennan
- International Agency for Research on Cancer, Lyon, France
| | - Paolo Boffetta
- Institute for Translational Epidemiology and Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York
| | - Sanford M Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Farin Kamangar
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, Maryland
| | - Christian C Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
| |
Collapse
|
|
15
|
Liu K, Zhang W, Chen X, Chen X, Yang K, Zhang B, Chen Z, Zhou Z, Hu J. Comparison on Clinicopathological Features and Prognosis Between Esophagogastric Junctional Adenocarcinoma (Siewert II/III Types) and Distal Gastric Adenocarcinoma: Retrospective Cohort Study, a Single Institution, High Volume Experience in China. Medicine (Baltimore) 2015; 94:e1386. [PMID: 26313779 PMCID: PMC4602903 DOI: 10.1097/md.0000000000001386] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 07/23/2015] [Accepted: 07/23/2015] [Indexed: 02/05/2023] Open
Abstract
The incidence of the EGJA is rapidly increasing. The clinicopathological features have not yet been elucidated. The aim of this study was to analyze the differences in clinicopathological features and prognosis between patients with esophagogastric junctional adenocarcinoma (EGJA) and distal gastric adenocarcinoma (DGA).In this retrospective study, 1230 patients who underwent gastrectomy between January 2006 and December 2010 in West China Hospital were enrolled. Patients were divided into 2 groups based on tumor location. Clinicopathological characteristics, postoperative complications, and survival outcomes were compared. Univariate and multivariate analysis were also used to evaluate the prognostic factors of DGA and EGJA.Patients with gastric adenocarcinoma were divided into 2 study groups according to tumor location: 321 EGJA (26.1%) and 909 DGA (73.9%). Tumors with larger diameter, more advanced pT and pN stage were more common in EGJA. Significant differences were revealed in 3-year overall survival rate (3-YS) between 2 groups: EGJA (57.5%) and DGA (65.5%) (P = 0.001), and further analysis indicate that there was also significant difference on 3-YS between EGJA (76.9%) and DGA (84.2%) (P = 0.012) in stage II. From our multivariate analysis, we found that there were different independent prognostic indicators for DGA and EGJA.The clinicopathological features of EGJA were strikingly different from DGA and patients with EGJA showed a worse prognosis when compared with DGA. The pT stage, pN stage, pM stage, tumor size, age, and radical degree were determined to be independent factors of prognosis for DGA, while only combined organ resection, pN stage, and pM stage were independent prognostic factors for EGJA.
Collapse
Affiliation(s)
- Kai Liu
- From the Department of Gastrointestinal Surgery (KL, WZ, XC, XC, KY, BZ, ZC, ZZ, JH); and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, PR China (KL, WZ, XC, XC, KY, JH)
| | | | | | | | | | | | | | | | | |
Collapse
|
|
16
|
Mukaisho KI, Nakayama T, Hagiwara T, Hattori T, Sugihara H. Two distinct etiologies of gastric cardia adenocarcinoma: interactions among pH, Helicobacter pylori, and bile acids. Front Microbiol 2015; 6:412. [PMID: 26029176 PMCID: PMC4426758 DOI: 10.3389/fmicb.2015.00412] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2015] [Accepted: 04/20/2015] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer can be classified as cardia and non-cardia subtypes according to the anatomic site. Although the gastric cancer incidence has decreased steadily in several countries over the past 50 years, the incidence of cardia cancers and esophageal adenocarcinoma (EAC) continue to increase. The etiological factors involved in the development of both cardia cancers and EACs are associated with high animal fat intake, which causes severe obesity. Central obesity plays roles in cardiac-type mucosa lengthening and partial hiatus hernia development. There are two distinct etiologies of cardia cancer subtypes: one associated with gastroesophageal reflux (GER), which predominantly occurs in patients without Helicobacter pylori (H. pylori) infection and resembles EAC, and the other associated with H. pylori atrophic gastritis, which resembles non-cardia cancer. The former can be developed in the environment of high volume duodenal content reflux, including bile acids and a higher acid production in H. pylori-negative patients. N-nitroso compounds, which are generated from the refluxate that includes a large volume of bile acids and are stabilized in the stomach (which has high levels of gastric acid), play a pivotal role in this carcinogenesis. The latter can be associated with the changing colonization of H. pylori from the distal to the proximal stomach with atrophic gastritis because a high concentration of soluble bile acids in an environment of low acid production is likely to act as a bactericide or chemorepellent for H. pylori in the distal stomach. The manuscript introduces new insights in causative factors of adenocarcinoma of the cardia about the role of bile acids in gastro-esophageal refluxate based upon robust evidences supporting interactions among pH, H. pylori, and bile acids.
Collapse
Affiliation(s)
- Ken-ichi Mukaisho
- Division of Molecular Diagnostic Pathology, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan
| | | | | | | | | |
Collapse
|
|
17
|
Pereira C, Barbosa RM, Laranjinha J. Dietary nitrite induces nitrosation of the gastric mucosa: the protective action of the mucus and the modulatory effect of red wine. J Nutr Biochem 2015; 26:476-83. [PMID: 25701398 DOI: 10.1016/j.jnutbio.2014.12.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 12/01/2014] [Accepted: 12/02/2014] [Indexed: 12/13/2022]
Abstract
The stomach chemical environment promotes the production of new molecules that can induce post-translational modifications of endogenous proteins with physiological impact. The nitrate-nitrite-nitric oxide pathway is relevant in this process via production of nitric oxide ((•)NO) and nitric oxide-derived nitrogen oxides (NOx) at high concentrations. Using a highly sensitive and selective chemiluminescence approach, we found that exposure the stomach of rats to nitrite yielded S- and N-nitroso derivatives in gastric mucus cysteine-rich glycoproteins (mucins). To lesser extent, the underlying epithelial cell layers also suffered nitrite-driven S- and N-nitroso modifications which increased upon mucus removal, indicating that, under normal nitrite load, (•)NO and NOx can reach inner layers of the stomach wall and locally modify proteins. S-nitrosation was by large the predominant modification. In vitro and ex vivo experiments indicated that the gastric nitrosation pattern is triggered by dietary nitrite in a concentration dependent manner, encompassing the intermediary formation of (•)NO and is susceptible to modulation by dietary reductants, notably red wine polyphenols. Collectively, these results suggest a protective action of the mucus and potential (•)NO-dependent biochemical effects at deeper cells layers of the mucosa.
Collapse
Affiliation(s)
- Cassilda Pereira
- Center for Neuroscience and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3000 Coimbra, Portugal
| | - Rui M Barbosa
- Center for Neuroscience and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3000 Coimbra, Portugal
| | - João Laranjinha
- Center for Neuroscience and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3000 Coimbra, Portugal.
| |
Collapse
|
|
18
|
Olefson S, Moss SF. Obesity and related risk factors in gastric cardia adenocarcinoma. Gastric Cancer 2015; 18:23-32. [PMID: 25209115 DOI: 10.1007/s10120-014-0425-4] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Accepted: 08/23/2014] [Indexed: 02/07/2023]
Abstract
Over recent decades, the incidence of cancers of the gastroesophageal junction, including gastric cardia tumors, has increased markedly. This is a trend that has been well documented, especially in studies from the USA and northern Europe that have also demonstrated a concomitant rise in the ratio of cardia to distal gastric cancers. The rise in the prevalence of gastric cardia adenocarcinoma has been paralleled by the worldwide obesity epidemic, with almost all epidemiological studies reporting increased body mass index and obesity increase the risk of cardia cancer development. However, the strength of this association is less marked than the link between obesity and esophageal adenocarcinoma, and the mechanisms remain poorly understood. Other possible confounders of the relationship between obesity and cardia cancer include the decline in Helicobacter pylori infection and the widespread use of proton pump inhibitors, although these have rarely been controlled for in case-control and cohort studies investigating associations between obesity and cardia cancer. We review these epidemiological trends and discuss proposed mechanisms for the association, drawing attention to controversies over the difficulty of defining cardia cancer. The relative paucity of high-quality epidemiological studies from other regions of the world should prompt further investigation of this issue, especially in populations undergoing rapid socioeconomic change.
Collapse
Affiliation(s)
- Sidney Olefson
- Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA
| | | |
Collapse
|
|
19
|
Castaño-Rodríguez N, Kaakoush NO, Mitchell HM. Pattern-recognition receptors and gastric cancer. Front Immunol 2014; 5:336. [PMID: 25101079 PMCID: PMC4105827 DOI: 10.3389/fimmu.2014.00336] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Accepted: 07/03/2014] [Indexed: 12/12/2022] Open
Abstract
Chronic inflammation has been associated with an increased risk of several human malignancies, a classic example being gastric adenocarcinoma (GC). Development of GC is known to result from infection of the gastric mucosa by Helicobacter pylori, which initially induces acute inflammation and, in a subset of patients, progresses over time to chronic inflammation, gastric atrophy, intestinal metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as pattern-recognition receptors (PRRs) are critical for generating mature pro-inflammatory cytokines that are crucial for both Th1 and Th2 responses. Given that H. pylori is initially targeted by PRRs, it is conceivable that dysfunction within genes of this arm of the immune system could modulate the host response against H. pylori infection, and subsequently influence the emergence of GC. Current evidence suggests that Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR5, and TLR9), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (NOD1, NOD2, and NLRP3), a C-type lectin receptor (DC-SIGN), and retinoic acid-inducible gene (RIG)-I-like receptors (RIG-I and MDA-5), are involved in both the recognition of H. pylori and gastric carcinogenesis. In addition, polymorphisms in genes involved in the TLR (TLR1, TLR2, TLR4, TLR5, TLR9, and CD14) and NLR (NOD1, NOD2, NLRP3, NLRP12, NLRX1, CASP1, ASC, and CARD8) signaling pathways have been shown to modulate the risk of H. pylori infection, gastric precancerous lesions, and/or GC. Further, the modulation of PRRs has been suggested to suppress H. pylori-induced inflammation and enhance GC cell apoptosis, highlighting their potential relevance in GC therapeutics. In this review, we present current advances in our understanding of the role of the TLR and NLR signaling pathways in the pathogenesis of GC, address the involvement of other recently identified PRRs in GC, and discuss the potential implications of PRRs in GC immunotherapy.
Collapse
Affiliation(s)
- Natalia Castaño-Rodríguez
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales , Sydney, NSW , Australia
| | - Nadeem O Kaakoush
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales , Sydney, NSW , Australia
| | - Hazel M Mitchell
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales , Sydney, NSW , Australia
| |
Collapse
|
|
20
|
Shim JH, Song KY, Jeon HM, Park CH, Jacks LM, Gonen M, Shah MA, Brennan MF, Coit DG, Strong VE. Is gastric cancer different in Korea and the United States? Impact of tumor location on prognosis. Ann Surg Oncol 2014; 21:2332-9. [PMID: 24599411 DOI: 10.1245/s10434-014-3608-7] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2013] [Indexed: 12/15/2022]
Abstract
PURPOSE To compare the characteristics and prognoses of gastric cancers by tumor location in Korean and U.S. subjects after curative-intent (R0) resection for gastric cancer (GC). METHODS Data were collected for all patients who had undergone R0 resection at one U.S. institution (n = 567) and one South Korean institution (n = 1,620). Patients with gastroesophageal junction tumors or neoadjuvant therapy were excluded. Patient, surgical, and pathologic variables were compared by tumor location. Factors associated with disease-specific survival (DSS) were determined via multivariate analysis. RESULTS In the Korean cohort, significantly more upper third GC (UTG) patients had undifferentiated, diffuse type, and advanced stage cancers compared to lower third GC (LTG) and middle third GC (MTG) patients. In the U.S. cohort, however, T stage was relatively evenly distributed among UTG, MTG, and LTG patients. The independent predictors of DSS in the Korean cohort were T stage, tumor size, retrieved and positive lymph node counts, and age, but in the U.S. cohort, the only independent predictors were T stage and positive lymph node count. Tumor size significantly affected DSS of Korean UTG patients but not U.S. UTG patients. CONCLUSIONS There were significant differences in tumor characteristics by tumor location within and between both national cohorts. On the basis of these findings, further study to investigate the biological difference between the two countries is needed.
Collapse
Affiliation(s)
- Jung Ho Shim
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
21
|
Yassibaş E, Arslan P, Yalçin S. Evaluation of dietary and life-style habits of patients with gastric cancer: a case-control study in Turkey. Asian Pac J Cancer Prev 2013. [PMID: 22901209 DOI: 10.7314/apjcp.2012.13.5.2291] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Gastric cancer is an important public health problem in the world and Turkey. In addition to Helicobacter pylori (H. pylori), smoking, alcohol consumption and family history, certain dietary factors have been associated with its occurrence. The impact of dietary habits and life-style factors on the risk of gastric cancer in Turkey were evaluated in this study. DESIGN A questionnaire was applied to 106 patients with gastric adenocarcinoma and 106 controls without cancer matched for age (range 28-85 years) and gender selected from a hospital based population. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated with logistic regression analysis. RESULTS The incidence of H. pylori was 81.3% in patients. Frequent consumption of salty dishes, very salty foods like pickles, soup mixes, sausages, foods at hot temperature (ORs=3.686, 7.784, 5.264, 3.148 and 3.273 respectively) and adding salt without tasting (OR=4.198) were associated with increased gastric risk. Also heavy smoking and high amount of alcohol consumption (p=0.000) were risk factors. Frequent consumption of green vegetables, onion, garlic and dried fruits (ORs=0.569, 0.092, 0.795 and 0.041) was non- significantly associated with decreased risk. CONCLUSION Improved dietary habits, reducing salt consumption and eradication of H. pylori infection may provide protection against gastric cancer in Turkey.
Collapse
Affiliation(s)
- Emine Yassibaş
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, Ankara, Turkey
| | | | | |
Collapse
|
|
22
|
Xiao ZY, Ru Y, Sun JT, Gao SG, Wang YF, Wang LD, Feng XS. Expression of CDX2 and villin in gastric cardiac intestinal metaplasia and the relation with gastric cardiac carcinogenesis. Asian Pac J Cancer Prev 2012; 13:247-50. [PMID: 22502678 DOI: 10.7314/apjcp.2012.13.1.247] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE To determine whether CDX2 and villin protein expression are associated with intestinal metaplasia (IM) in gastric cardiac mucosa and to explore the relationship with evolution of gastric cardiac adenocarcinoma (GCA). METHODS We studied 143 gastric cardiac biopsy or resection specimens from Henan province China, including 25 cardiac gastritis specimens with IM, 65 dysplasia specimens with IM and 35 gastric cardiac adenocarcinoma specimens and stained them for CDX2 and villin by the immunohistochemical SP method. 15 normal gastric cardiac biopsy specimens were also collected as control. RESULTS (1) Normal gastric mucosa presented no CDX2 and villin expression. The positive rates of CDX2 protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissues were 84.0% (21/25), 66.7% (32/48) and 36.4% (20/55), respectively. While the positive rates of villin protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissues were 76.0% (19/25), 70.8% (34/48) and 45.5% (25/55), respectively.There were significant differences among the three groups for both CDX2 and villin (P<0.01). Spearman's rank correlation coefficient(rho) showed a close correlation between the two proteins (r=0.843, P<0.01) and both were positively related with tumor differentiation (both P<0.05), but not associated with age, sex, invasion and metastasis of lymph node (P>0.05). CONCLUSION Our results suggest that ectopic expression of CDX2 and villin may be involved in early-stage IM and tumorigenesis in gastric cardia and the expression of villin may be regulated by CDX2.
Collapse
Affiliation(s)
- Zhong-Yue Xiao
- Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
| | | | | | | | | | | | | |
Collapse
|
|
23
|
Felley C, Bouzourene H, VanMelle MBG, Hadengue A, Michetti P, Dorta G, Spahr L, Giostra E, Frossard JL. Age, smoking and overweight contribute to the development of intestinal metaplasia of the cardia. World J Gastroenterol 2012; 18:2076-83. [PMID: 22563195 PMCID: PMC3342606 DOI: 10.3748/wjg.v18.i17.2076] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2011] [Revised: 01/04/2012] [Accepted: 02/26/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the role of Helicobacter pylori (H. pylori), gastroesophageal reflux disease (GERD), age, smoking and body weight on the development of intestinal metaplasia of the gastric cardia (IMC).
METHODS: Two hundred and seventeen patients scheduled for esophagogastroduodenoscopy were enrolled in this study. Endoscopic biopsies from the esophagus, gastroesophageal junction and stomach were evaluated for inflammation, the presence of H. pylori and intestinal metaplasia. The correlation of these factors with the presence of IMC was assessed using logistic regression.
RESULTS: IMC was observed in 42% of the patients. Patient age, smoking habit and body mass index (BMI) were found as potential contributors to IMC. The risk of developing IMC can be predicted in theory by combining these factors according to the following formula: Risk of IMC = a + s - 2B where a = 2,…6 decade of age, s = 0 for non-smokers or ex-smokers, 1 for < 10 cigarettes/d, 2 for > 10 cigarettes/d and B = 0 for BMI < 25 kg/m2 (BMI < 27 kg/m2 in females), 1 for BMI > 25 kg/m2 (BMI > 27 kg/m2 in females). Among potential factors associated with IMC, H. pylori had borderline significance (P = 0.07), while GERD showed no significance.
CONCLUSION: Age, smoking and BMI are potential factors associated with IMC, while H. pylori and GERD show no significant association. IMC can be predicted in theory by logistic regression analysis.
Collapse
|
|
24
|
Jang JH, Beron RI, Ahn HS, Kong SH, Lee HJ, Kim WH, Lee KU, Yang HK. Clinicopathological Features of Upper Third Gastric Cancer during a 21-Year Period (Single Center Analysis). J Gastric Cancer 2010; 10:212-8. [PMID: 22076188 PMCID: PMC3204506 DOI: 10.5230/jgc.2010.10.4.212] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2010] [Accepted: 10/12/2010] [Indexed: 12/11/2022] Open
Abstract
Purpose The aim of this study was to determine proportions of upper third gastric cancer (UTG) among all gastric cancers and analyze clinicopathological features of the disease. Materials and Methods The medical records of 12,300 patients who underwent gastric surgery between 1986 and 2006 at Seoul National University Hospital (SNUH) were retrospectively reviewed. Clinicopathological features of 1,260 patients with UTG and 9,929 patients with middle or lower third gastric cancer (MLG) were compared, and annual proportions of UTG were evaluated. Results The proportion of patients with UTG rapidly increased from 2.6% in 1986 to 12.5% in 1992. However, linear regression analysis showed that the rate of increase was reduced (0.21%/year) after 1992 (12.5% to 14.2% from 1992 to 2006). Compared with the MLG group, the UTG group had a lower proportion of (22.3% vs. 39.7%, P<0.001) and a greater proportion of stage III/IV disease (39.4% vs. 31.7%, P<0.001). The UTG group also had larger tumors than the MLG group in stages I/II and III (3.5 cm/5.3 cm/6.5 cm vs. 3.2 cm/5.0 cm/5.8 cm, P=0.020/0.028 /<0.001), a higher proportion of undifferentiated cancer (63.1% vs. 53.7%, P<0.001), and less intestinal Lauren's type (38.8% vs. 47.4%, P<0.001). The 5-year survival rate of the UTG group was significantly lower than that of the MLG group in stages I/II and III (85.6%/63.1%/34.2% vs. 91.6%/ 69.2%/44.7%, P<0.001/0.028/0.006). Conclusions The proportion of UTGs has increased over the last two decades at SNUH, but the rate of increase has been greatly reduced since 1992. The UTG group showed a poorer prognosis compared with the MLG group in stages I/II and III.
Collapse
Affiliation(s)
- Je-Ho Jang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Hishida A, Matsuo K, Goto Y, Naito M, Wakai K, Tajima K, Hamajima N. No associations of Toll-like receptor 2 (TLR2) -196 to -174del polymorphism with the risk of Helicobacter pylori seropositivity, gastric atrophy, and gastric cancer in Japanese. Gastric Cancer 2010; 13:251-7. [PMID: 21128061 DOI: 10.1007/s10120-010-0567-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Accepted: 07/20/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND Recently, the association between gastric cancer risk and a functional polymorphism of Toll-like receptor 2 (TLR2), -196 to -174del, was reported for a Japanese population. This study aimed to confirm the associations of the polymorphism with the risk of gastric cancer, as well as Helicobacter pylori seropositivity and the risk of gastric atrophy in Japanese. METHODS The study subjects were 583 histologically diagnosed gastric cancer patients and 1636 age- and sex-frequency-matched control outpatients who visited Aichi Cancer Center Hospital from the years 2001 to 2005. Serum anti-H. pylori IgG antibody and pepsinogens were measured to evaluate H. pylori infection and gastric atrophy, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a logistic model. RESULTS The age- and sex-adjusted ORs of gastric cancer were 1.13 (95% CI: 0.88-1.46) for ins/del, 1.17 (95% CI: 0.79-1.73) for del/del, and 1.14 (95% CI: 0.89-1.45) for ins/del + del/del, relative to the ins/ins genotype compared with gastric atrophy controls; none of these findings were statistically significant. The TLR2 -196 to 174del polymorphism was not significantly associated with either H. pylori seropositivity or gastric atrophy. CONCLUSION Our study did not reproduce the association between gastric cancer risk and the TLR2 -196 to -174del polymorphism in Japanese. Further examinations with sufficient numbers of study subjects are required to verify our findings.
Collapse
Affiliation(s)
- Asahi Hishida
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Japan
| | | | | | | | | | | | | |
Collapse
|
|
26
|
Epidemiological aspects of gastric adenocarcinoma: are predictive diagnostics and targeted preventive measures possible? EPMA J 2010. [PMID: 23199088 PMCID: PMC3405336 DOI: 10.1007/s13167-010-0043-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The incidence of gastric cancer has witnessed major changes over the past decades. Until recently, gastric cancer was a common malignancy in most countries. A striking decline in incidence in most Western populations has occurred since the 1970s, and elucidating the detailed causes for this trend can potentially be of great value for targeted preventive measures. Furthermore, it can add to the understanding of malignant disease and prevention in general. Moreover, the absolute number of cases worldwide is predicted to increase during many years to come. Gastric cancer is typically diagnosed at an advanced stage in symptomatic patients, and there are often no effective curative or palliative or therapeutic options. This fact highlights the need for research aiming to increase our understanding of the etiology of this cancer, facilitating the design of successful targeted preventive strategies for different populations. The future outlook in terms of decreasing gastric cancer deaths would be to identify such intelligent diagnostic tools. In this article, we present a summary of the epidemiology of gastric cancer, with special focus on its etiology.
Collapse
|
|
27
|
Cervantes DT, Fischbach LA. Gastric cardia adenocarcinoma in Taiwanese men: Positive associations due to selection bias. World J Gastroenterol 2010; 16:1553-4. [PMID: 20333802 PMCID: PMC2846267 DOI: 10.3748/wjg.v16.i12.1553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The factors associated with an increase in gastric cardia adenocarcinoma are poorly understood. Environmental factors such as Helicobacter pylori (H. pylori) infection and diet have been hypothesized to play a role in the recently increased risk of this disease, but additional studies are needed. In conducting studies to establish the relationship between potential risk factors and gastric cardia adenocarcinoma, it is necessary to carefully consider the role of bias. In a recently published study, the reported associations between H. pylori as well as post-meal physical exertion and gastric cardia adenocarcinoma may have been greatly influenced by selection bias.
Collapse
|
|
28
|
Hishida A, Matsuo K, Goto Y, Mitsuda Y, Hiraki A, Naito M, Wakai K, Tajima K, Hamajima N. No association between AICDA 7888 C/T polymorphism, Helicobacter pylori seropositivity, and the risk of atrophic gastritis and gastric cancer in Japanese. Gastric Cancer 2010; 13:43-9. [PMID: 20373075 DOI: 10.1007/s10120-009-0534-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2009] [Accepted: 12/02/2009] [Indexed: 02/07/2023]
Abstract
BACKGROUND The aberrant expression of activation-induced cytidine deaminase (AICDA) was reportedly induced in gastric epithelial cells infected with cytotoxin-associated gene A (cagA)-positive Helicobacter pylori, resulting in the accumulation of alterations in the TP53 tumor suppressor gene in gastric cells. We investigated the association of the AICDA 7888 C/T polymorphism with H. pylori infection and the risk of gastric cancer and atrophic gastritis in Japanese subjects. METHODS The study subjects were 583 histologically diagnosed gastric cancer patients (cases) and 1637 age- and sex-frequency-matched control outpatients, who visited Aichi Cancer Center Hospital from the years 2001 to 2005. In the controls, serum anti-H. pylori IgG antibody and pepsinogens were measured to evaluate H. pylori infection and atrophic gastritis, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a logistic model. RESULTS H. pylori seropositivity in the controls was not significantly associated with the AICDA 7888 C/T genotypes. Among the H. pylori seropositive control subjects, the age and sex-adjusted ORs of atrophic gastritis were not statistically significant: 0.84 (95% CI, 0.62-1.13) for C/T, 0.82 (95% CI, 0.56-1.21) for T/T, and 0.83 (95% CI, 0.63-1.11) for C/T+T/T, relative to the C/C genotype. The age- and sex-adjusted ORs of gastric cancer relative to atrophic gastritis were also not statistically significant, at 1.17 (95% CI 0.89-1.54), 1.21 (95% CI, 0.85-1.71), and 1.18 (95% CI, 0.91-1.53), respectively. The OR of gastric cancer cases compared with the whole cohort of control subjects was also not significant. CONCLUSION The hypothetical association of the AICDA 7888 C/T polymorphism with the risk of gastric cancer or gastric atrophy was not shown in this study.
Collapse
Affiliation(s)
- Asahi Hishida
- Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Stromal regulatory T-cells are associated with a favourable prognosis in gastric cancer of the cardia. BMC Gastroenterol 2009; 9:65. [PMID: 19732435 PMCID: PMC2749861 DOI: 10.1186/1471-230x-9-65] [Citation(s) in RCA: 125] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2009] [Accepted: 09/04/2009] [Indexed: 12/22/2022] Open
Abstract
Background Recent evidence suggests that CD4+CD25+FoxP3+ regulatory T-cells (Treg) may be responsible for the failure of host anti-tumour immunity by suppressing cytotoxic T- cells. We assessed the prognostic significance of tumour infiltrating lymphocytes (TIL) in intestinal-type gastric cardiac cancer. Methods Tumour infiltrating lymphocyte (TIL) subsets and tumour infiltrating macrophages (TIM) were investigated in 52 cases using tissue microarrays. The interrelationship between the cell populations (CD3+, CD8+, CD20+, CD68+, GranzymeB+, FoxP3+) in different compartments and NED-survival was investigated (median follow-up time: 61 months). Results Intraepithelial infiltration with TIL and TIM including Treg was generally low and not related to NED-survival. However, patients with large numbers of FoxP3+ Treg in the tumour stroma (>125.9 FoxP3+TILs/mm2) had a median survival time of 58 months while those with low FoxP3+ TIL counts (<125.9 FoxP3+TILs/mm2) had a median survival time of 32 months (p = 0.006). Patients with high versus low stromal CD68+/FoxP3+ cell ratios in primary tumour displayed median survivals of 32 and 55 months, respectively (p = 0.008). Conclusion Our results suggest that inflammatory processes within the tumour stroma of gastric intestinal-type adenocarcinomas located at the gastric cardia may affect outcome in two ways. Tumour-infiltrating macrophages are likely to promote carcinogenesis while large numbers of Treg are associated with improved outcome probably by inhibiting local inflammatory processes promoting carcinogenesis. Thus, inhibition of Treg may not be a feasible treatment option in gastric adenocarcinoma.
Collapse
|
|
30
|
Bhargava S, Hotz B, Buhr HJ, Hotz HG. An orthotopic nude mouse model for preclinical research of gastric cardia cancer. Int J Colorectal Dis 2009; 24:31-9. [PMID: 18825389 DOI: 10.1007/s00384-008-0584-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/10/2008] [Indexed: 02/04/2023]
Abstract
PURPOSE A clinically relevant animal model for cancer of the esophagogastric junction does not exist. This study aimed to establish an orthotopic mouse model for human gastric cancer of the distal stomach and the gastric cardia. MATERIALS AND METHODS Human gastric cancer cell lines AGS, MKN-45, and NCI-N87 were injected subcutaneously into nude mice. These donor tumors were harvested after 4 weeks and minced into small tumor fragments. One donor tumor fragment was orthotopically implanted into the submucosa of either gastric cardia or distal stomach in other mice. The animals were killed 4, 8, and 12 weeks after tumor implantation. Volume of the primary tumor and local and systemic tumor spread were determined. RESULTS The implantation technique resulted in a tumor take rate of 100%. An artificial dissemination of tumor cells into the abdominal cavity due to the procedure was not observed. CONCLUSIONS We report for the first time the development of a clinically relevant mouse model for human gastric cancer of the gastric cardia and the distal stomach. Primary tumor growth and local and systemic spread progressed continuously during the observation period and mimic the human situation of this disease. This model may be suitable to evaluate novel treatment strategies for this malignancy.
Collapse
Affiliation(s)
- Sarah Bhargava
- Department of Surgery, Charité School of Medicine Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | | | | | | |
Collapse
|
|
31
|
Carboni F, Lorusso R, Santoro R, Lepiane P, Mancini P, Sperduti I, Santoro E. Adenocarcinoma of the esophagogastric junction: the role of abdominal-transhiatal resection. Ann Surg Oncol 2008; 16:304-10. [PMID: 19050964 DOI: 10.1245/s10434-008-0247-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2008] [Revised: 10/01/2008] [Accepted: 10/28/2008] [Indexed: 12/23/2022]
Abstract
The surgical strategy for adenocarcinoma of the esophagogastric junction is still controversial. The aim of this study was to evaluate surgical results of the abdominal-transhiatal approach for 100 consecutively operated type II and III cardia adenocarcinoma, to clarify clinicopathological differences between these tumors, and to define prognostic factors. A prospectively maintained database identified 100 consecutively operated patients with Siewert type II and III cardia adenocarcinoma. Survival was analyzed by the Kaplan-Meier method. Differences between subgroups and prognostic factors were evaluated by the log rank test and Cox regression. Concerning clinicopathological characteristics, only the incidence of T1-2 stage was significantly higher in Siewert II type (P = .006). A complete (R0) resection was obtained in 74 patients (74%). Overall postoperative mortality and morbidity rates were 6% and 28%, respectively. Overall actuarial 5-year survival rate in resected patients was 27.4% (median 27 months), with 20.6% for type II and 34 for type III cancers (P = .07). Considering R0 resections, overall actuarial 5-year survival rate was 33.9% (median 33 months), with 26.7% for type II and 40.5 for type III cancer (P = .06). Pathologic T and N stage and R status were independent prognostic factors by multivariate analysis, and Siewert type showed a trend toward significance. The abdominal-transhiatal approach is a safe surgical approach, allowing complete tumor resection and adequate lymphadenectomy in these patients. True carcinoma of the cardia may be a distinct clinical entity with a more aggressive natural history than subcardial gastric carcinoma.
Collapse
Affiliation(s)
- Fabio Carboni
- Department of Digestive Surgery, Regina Elena Cancer Institute, Rome, Italy.
| | | | | | | | | | | | | |
Collapse
|
|
32
|
Maeda H, Okabayashi T, Nishimori I, Sugimoto T, Namikawa T, Dabanaka K, Tsujii S, Onishi S, Kobayashi M, Hanazaki K. Clinicopathologic features of adenocarcinoma at the gastric cardia: is it different from distal cancer of the stomach? J Am Coll Surg 2008; 206:306-310. [PMID: 18222384 DOI: 10.1016/j.jamcollsurg.2007.06.306] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2007] [Revised: 06/09/2007] [Accepted: 06/20/2007] [Indexed: 02/08/2023]
Abstract
BACKGROUND Although the incidence of gastric cardia cancer is considerably less than more distal gastric cancer, the rate of occurrence is now increasing. The objective of this study was to evaluate and compare the clinicopathologic findings of gastric cardia and more distal stomach adenocarcinoma. STUDY DESIGN Patients included in our study were those who underwent operations for gastric adenocarcinoma in our institute from 1981 to 2006, and who had undergone complete medical history, including history of daily alcohol consumption; smoking; body mass index; and pathologic examinations. A total of 843 patients were included in our study, and were divided into cardia and noncardia cancer groups. RESULTS Among the 843 patients, 23 (2.8%) had gastric cardia cancer. There were no substantial differences in age, gender, body mass index, smoking, or alcohol consumption between the two groups. Mean size of cardia tumors was larger than noncardia tumors. Although noncardia cancer was often detected at an early stage, gastric cardia cancer was most often diagnosed at an advanced stage. Pathologically, cardia cancer was more invasive and had more lymphatic permeation and lymph node metastasis than noncardia cancer. CONCLUSIONS Gastric cardia cancer occurs at a low incidence of only 2.8% of resected gastric cancers. Unlike cases of gastric cardia cancer in Western populations, body mass index is not associated with occurrence of gastric cardia cancer in our study. Because gastric cardia cancer appears more aggressive than noncardia gastric cancer, early diagnosis and intervention are important.
Collapse
|
|
33
|
van Blankenstein M, Looman CWN, Siersema PD, Kuipers EJ, Coebergh JWW. Trends in the incidence of adenocarcinoma of the oesophagus and cardia in the Netherlands 1989-2003. Br J Cancer 2007; 96:1767-71. [PMID: 17505507 PMCID: PMC2359916 DOI: 10.1038/sj.bjc.6603798] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Over the 15-year period 1989–2003, the incidence of oesophagus–cardia adenocarcinoma in the Netherlands rose annually by 2.6% for males and 1.2% for females. This was the net outcome of annual increases in the incidence of adenocarcinoma of the oesophagus (ACO) of 7.2% for males and 3.5% for females and annual declines in the incidence of adenocarcinoma of the gastric cardia (AGC) of more than 1% for both genders. Nonlinear cohort patterns were found in females with ACO and for both genders in AGC; a nonlinear period pattern was observed only in males with AGC. These differing epidemiological patterns for ACO and AGC do not support a common aetiology. Proposed underlying factors for the rise in ACO incidence appear to have little effect on AGC incidence. This and the secular decline in smoking among males may have led to the decline in AGC incidence.
Collapse
Affiliation(s)
- M van Blankenstein
- Department of Gastroenterology and Hepatology, Erasmus MC, Erasmus University Medical Centre, Rotterdam, The Netherlands.
| | | | | | | | | |
Collapse
|
|
34
|
Abstract
Gastric cancer remains a major health burden on many societies claiming hundreds of thousands of lives every year. The discovery of Helicobacter pylori has no doubt revolutionised our understanding of this malignancy, which is now regarded as a paradigm for infection-induced chronic inflammation-mediated cancer. In this paper, we discuss the evidence for the association between H. pylori and gastric adenocarcinoma and MALT lymphoma. We also discuss the pathogenesis of these two forms of cancer and the factors that determine their outcome. There is no doubt that the knowledge accumulated over the past two decades will be translated into eventual victory over this killer cancer, largely because we now appreciate that the best way to prevent the cancer is by preventing acquisition of the infection in the first place, or by eradicating the infection in infected subjects. Defining the optimal timing of intervention is going to be the challenge facing us over the next two decades.
Collapse
|