Epidemiology of Gallbladder Disease: Cholelithiasis and Cancer

PubMed Central

Stinton, Laura M.

2012-01-01

Diseases of the gallbladder are common and costly. The best epidemiological screening method to accurately determine point prevalence of gallstone disease is ultrasonography. Many risk factors for cholesterol gallstone formation are not modifiable such as ethnic background, increasing age, female gender and family history or genetics. Conversely, the modifiable risks for cholesterol gallstones are obesity, rapid weight loss and a sedentary lifestyle. The rising epidemic of obesity and the metabolic syndrome predicts an escalation of cholesterol gallstone frequency. Risk factors for biliary sludge include pregnancy, drugs like ceftiaxone, octreotide and thiazide diuretics, and total parenteral nutrition or fasting. Diseases like cirrhosis, chronic hemolysis and ileal Crohn's disease are risk factors for black pigment stones. Gallstone disease in childhood, once considered rare, has become increasingly recognized with similar risk factors as those in adults, particularly obesity. Gallbladder cancer is uncommon in developed countries. In the U.S., it accounts for only ~ 5,000 cases per year. Elsewhere, high incidence rates occur in North and South American Indians. Other than ethnicity and female gender, additional risk factors for gallbladder cancer include cholelithiasis, advancing age, chronic inflammatory conditions affecting the gallbladder, congenital biliary abnormalities, and diagnostic confusion over gallbladder polyps. PMID:22570746

Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer

ClinicalTrials.gov

2018-04-27

Extrahepatic Bile Duct Adenocarcinoma, Biliary Type; Gallbladder Adenocarcinoma, Biliary Type; Metastatic Pancreatic Adenocarcinoma; Recurrent Cholangiocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Intrahepatic Cholangiocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Gallbladder Cancer AJCC V7; Stage III Hepatocellular Carcinoma AJCC v7; Stage III Intrahepatic Cholangiocarcinoma AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Gallbladder Cancer AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7; Stage IVB Gallbladder Cancer AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Carcinoma

Gallbladder cancer: review of a rare orphan gastrointestinal cancer with a focus on populations of New Mexico.

PubMed

Nemunaitis, Jacklyn M; Brown-Glabeman, Ursa; Soares, Heloisa; Belmonte, Jessica; Liem, Ben; Nir, Itzhak; Phuoc, Victor; Gullapalli, Rama R

2018-06-18

Gallbladder cancer is a rare malignancy of the biliary tract with a poor prognosis, frequently presenting at an advanced stage. While rare in the United States overall, gallbladder cancer has an elevated incidence in geographically distinct locations of the globe including Chile, North India, Korea, Japan and the state of New Mexico in the United States. People with Native American ancestry have a much elevated incidence of gallbladder cancer compared to Hispanic and non-Hispanic white populations of New Mexico. Gallbladder cancer is also one of the few bi-gendered cancers with an elevated female incidence compared to men. Similar to other gastrointestinal cancers, gallbladder cancer etiology is likely multi-factorial involving a combination of genomic, immunological, and environmental factors. Understanding the interplay of these unique epidemiological factors is crucial in improving the prevention, early detection, and treatment of this lethal disease. Previous studies have failed to identify a distinct genomic mutational profile in gallbladder cancers, however, work to identify promising clinically actionable targets is this form of cancer is ongoing. Examples include, interest in the HER2/Neu signaling pathway and the recognition that chronic inflammation plays a crucial role in gallbladder cancer pathogenesis. In this review, we provide a comprehensive overview of gallbladder cancer epidemiology, risk factors, pathogenesis, and treatment with a specific focus on the rural and Native American populations of New Mexico. We conclude this review by discussing future research directions with the goal of improving clinical outcomes for patients of this lethal malignancy.

Circular RNA HIPK3 promotes gallbladder cancer cell growth by sponging microRNA-124.

PubMed

Kai, Ding; Yannian, Liao; Yitian, Chen; Dinghao, Gong; Xin, Zhao; Wu, Ji

2018-06-18

Recent studies have implied that circHIPK3, an abundant circular RNA (circRNA), participates in tumorigenesis and cancer progression. Its expression and potential functions in human gallbladder cancer were examined in this study. We show that circHIPK3 is upregulated in human gallbladder cancer cells. But its level is low in gallbladder epithelial cells. circHIPK3 silencing by targeted siRNA potently inhibited survival and proliferation of established and primary human gallbladder cancer cells, while inducing cell apoptosis. Conversely, ectopic over-expression of circHIPK3 can further promote cancer cell proliferation. In gallbladder cancer cells, circHIPK3 sponged the tumor-suppressive microRNA-124 (miR-124) to sequester and inhibit its activity, thereby leading to increased expression of miR-124 targets, including ROCK1 (rho-associated protein kinase 1) and CDK6 (rho-associated protein kinase). Ectopic over-expression of miR-124 b y a lentiviral vector mimicked and abolished actions by circHIPK3 siRNA in gallbladder cancer cells. At last, we show that circHIPK3 is upregulated in human gallbladder cancer tissues, which is correlated with miR-124 downregulation and ROCK1-CDK6 upregulation. Together, we conclude that circHIPK3 promotes gallbladder cancer cell growth possibly by sponging miR-124. The over-expressed circHIPK3 could be a novel therapeutic target and diagnosis marker of human gallbladder cancer. Copyright © 2018. Published by Elsevier Inc.

Imaging and Screening of Cancer of the Gallbladder and Bile Ducts.

PubMed

Sandrasegaran, Kumar; Menias, Christine O

2017-11-01

Biliary cancers include gallbladder cancer (GBC) and cholangiocarcinoma (CCA). GBC may appear as a mass replacing the gallbladder, thickened gallbladder wall, or polypoid lesion in the gallbladder. Gallbladder polyps with low risk of GBC (eg, 6- to 10-mm polyps without other risk factors) are screened with sonography. In general, polyps smaller than 5 mm are ignored and those larger than 10 mm require surgical consideration. Screening for CCA is less well-established. On imaging, CCA may be divided into mass-forming, periductal infiltrating, and intraductal types. This review discusses the current state of screening and diagnosis of GBC and CCA. Copyright © 2017 Elsevier Inc. All rights reserved.

Laparoscopic completion radical cholecystectomy for T2 gallbladder cancer.

PubMed

Gumbs, Andrew A; Hoffman, John P

2010-12-01

The role of minimally invasive surgery in the surgical management of gallbladder cancer is a matter of controversy. Because of the authors' growing experience with laparoscopic liver and pancreatic surgery, they have begun offering patients laparoscopic completion partial hepatectomies of the gallbladder bed with laparoscopic hepatoduodenal lymphadenectomy. The video shows the steps needed to perform laparoscopic resection of the residual gallbladder bed, the hepatoduodenal lymph node nodes, and the residual cystic duct stump in a setting with a positive cystic stump margin. The skin and fascia around the previous extraction site are resected, and this site is used for specimen retrieval during the second operation. To date, three patients have undergone laparoscopic radical cholecystectomy with hepatoduodenal lymph node dissection for gallbladder cancer. The average number of lymph nodes retrieved was 3 (range, 1-6), and the average estimated blood loss was 117 ml (range, 50-200 ml). The average operative time was 227 min (range, 120-360 min), and the average hospital length of stay was 4 days (range, 3-5 days). No morbidity or mortality was observed during 90 days of follow-up for each patient. Although controversy exists as to the best surgical approach for gallbladder cancer diagnosed after routine laparoscopic cholecystectomy, the minimally invasive approach seems feasible and safe, even after previous hepatobiliary surgery. If the previous extraction site cannot be ascertained, all port sites can be excised locally. Larger studies are needed to determine whether the minimally invasive approach to postoperatively diagnosed early-stage gallbladder cancer has any drawbacks.

Gallbladder Cancer—Health Professional Version

Cancer.gov

Cancer that arises in the gallbladder is uncommon. Almost all gallbladder cancers are adenocarcinomas. The most common symptoms caused by gallbladder cancer are jaundice, pain, and fever. Find evidence-based information on gallbladder cancer treatment.

Cancer of the gallbladder-Chilean statistics.

PubMed

Villanueva, Luis

2016-01-01

Chile has the world's highest rate of incidence as well as death from cancer of the gallbladder and biliary ducts. The problem is most acute in the southern provinces. These areas constitute the low average income associated with low educational attainment and a high rate of obesity compared with the rest of Chile. We could also include genetic factors related to processes of lithogenesis to these elements which are more common among the Mapuche. This population sub-group could benefit from special government programmes for early diagnosis and treatment of lithiasic disease and for the management of risk factors such as obesity. In this way, we could reduce the mortality rate of gallbladder cancer.

High-resolution sonography for distinguishing neoplastic gallbladder polyps and staging gallbladder cancer.

PubMed

Kim, Jung Hoon; Lee, Jae Young; Baek, Jee Hyun; Eun, Hyo Won; Kim, Young Jae; Han, Joon Koo; Choi, Byung Ihn

2015-02-01

OBJECTIVE. The purposes of this study were to compare staging accuracy of high-resolution sonography (HRUS) with combined low- and high-MHz transducers with that of conventional sonography for gallbladder cancer and to investigate the differences in the imaging findings of neoplastic and nonneoplastic gallbladder polyps. MATERIALS AND METHODS. Our study included 37 surgically proven gallbladder cancer (T1a = 7, T1b = 2, T2 = 22, T3 = 6), including 15 malignant neoplastic polyps and 73 surgically proven polyps (neoplastic = 31, nonneoplastic = 42) that underwent HRUS and conventional transabdominal sonography. Two radiologists assessed T-category and predefined polyp findings on HRUS and conventional transabdominal sonography. Statistical analyses were performed using chi-square and McNemar tests. RESULTS. The diagnostic accuracy for the T category was T1a = 92-95%, T1b = 89-95%, T2 = 78-86%, and T3 = 84-89%, all with good agreement (κ = 0.642) using HRUS. The diagnostic accuracy for differentiating T1 from T2 or greater than T2 was 92% and 89% on HRUS and 65% and 70% with conventional transabdominal sonography. Statistically common findings for neoplastic polyps included size greater than 1 cm, single lobular surface, vascular core, hypoechoic polyp, and hypoechoic foci (p < 0.05). The value of HRUS in the differential diagnosis of a gallbladder polyp was more clearly depicted internal echo foci than conventional transabdominal sonography (39 vs 21). A polyp size greater than 1 cm was independently associated with a neoplastic polyp (odds ratio = 7.5, p = 0.02). The AUC of a polyp size greater than 1 cm was 0.877. The sensitivity and specificity were 66.67% and 89.13%, respectively. CONCLUSION. HRUS is a simple method that enables accurate T categorization of gallbladder carcinoma. It provides high-resolution images of gallbladder polyps and may have a role in stratifying the risk for malignancy.

Quality of Life in Patients Undergoing Radiation Therapy for Primary Lung Cancer, Head and Neck Cancer, or Gastrointestinal Cancer

ClinicalTrials.gov

2017-05-23

Anal Cancer; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Pancreatic Cancer; Small Intestine Cancer

[Cancer of the gallbladder in Chile].

PubMed

Nervi, F

2001-09-01

This issue of the Revista brings two articles relayed to gallbladder cancer (GC), a highly prevalent cancer among Chileans. The first papaer relates to therapy for Stage II NO GC. Authors from Universidad de la Frontera corroborate the bad results usually obatined with adjunct chemotheraphy and radiotheraphy, associated to a second operation. The second paper discusses the negative influences that the new Xth Edition of the International Classification of Diseases might have on GC control. This cancer appears now with a dramatic 100% decrease in mortality rate in the last 3 years, associated to a simultaneous increase of the digit related to biliary tract cancer of "undefined orgin", which in the great majority of cases truly corresponds to GC throughout the world. This involuntary bias could have a strong negative effect on health policy makers, because health resources will not be derived to perform more cholecystectomies needed to significantly decrease the number of gallbladders at risk. This is a major issue for the Chilean health system, since GC represents the first cause of deaths due to cancer among Chilean women.

Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

ClinicalTrials.gov

2013-01-24

Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

Diagnosis of incidental gallbladder cancer after laparoscopic cholecystectomy: our experience

PubMed Central

2013-01-01

Background Gallbladder carcinoma is a rare high malignancy neoplasm. The incidence of intra or post-operative incidental gallbladder carcinoma diagnosis is estimated between 0,2 and 2,8%. Primary aim of our study is to evaluate incidental gallbladder carcinoma's incidence in our experience. Methods We retrospectively reviewed our Surgery Division's experience about the totality of laparoscopic cholecystectomies with post-operative histological evidence of incidental gallbladder cancer. We evaluated patients' characteristics, surgical related variables, histological response, surgivcal radicalization characteristics and surgical outcome. Results In the considered sample we observed 7 accidental gallbladder adenocarcinomas in post-operative histological examination. Pathological results were:1 pT1b N0 (G1), 2 pT2 N0 (G2), 2 pT2 N1 (G3b), 2 pT3 N1 (G3b) (Table 1). In 5 cases we performed neoplasm radicalization surgery with standard procedure revision. Two patients died before radicalization. Median global survival was 34 months. Conclusion With the increase of laparoscopic cholecystectomies both elective and urgent performed in our centre we observed also an increase of incidentally diagnosed gallbladder neoplasms. Early diagnosis, meticulous peri-operative study and accurate surgical strategy are essential factors to obtain good results in incidental gallbladder cancer. PMID:24268097

Gallbladder Cancer—Patient Version

Cancer.gov

Gallbladder cancer is a rare cancer that is usually diagnosed late due a to lack of early signs and symptoms. It is sometimes found when the gallbladder is checked for gallstones or removed. Start here to find information on gallbladder cancer treatment.

Gallstones and gallbladder cancer-volume and weight of gallstones are associated with gallbladder cancer: a case-control study.

PubMed

Roa, Iván; Ibacache, Gilda; Roa, Juan; Araya, Juan; de Aretxabala, Xabier; Muñoz, Sergio

2006-06-15

Gallstones are considered the most important risk factor for gallbladder cancer. To identify differences in the number, weight, volume, and density of gallstones associated with chronic cholecystitis (CC), gallbladder dysplasia (GD), and gallbladder cancer (GBC). A total of 125 cases were selected, of which 93 had gallstones associated with GBC and 31 had gallstones associated with GD. The controls were those with CC, matched by sex and age. The number, weight, volume, and density of these gallstones were examined in order to determine differences and relative cancer risk. Number: Multiple gallstones were present in over 76% of cases (GBC and GD) and controls (P = ns). The average number of multiple stones was 21 in GBC versus 14 in controls (P < 0.01). Weight: The average weight of the gallstones was 9.6 g in GBC versus 6.0 g in controls (P = 0.0004). The average weight in multiple stones over 10 g had strong association with GBC (P = 0.0006). Volume: The average volume was 11.7 and 6.48 ml in GBC and controls (P = 0.0002). Average volumes of 6, 8, and 10 ml had a relative cancer risk of 5, 7, and 11 times, respectively. Size: No differences were shown between GBC, GD, and controls. The volume of gallstones associated with other risk factors of GBC may be helpful in prioritizing cholecystectomies in symptomatic patients. Copyright 2006 Wiley-Liss, Inc.

Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression.

PubMed

Huang, Feng; Wang, Mei; Yang, Tingting; Cai, Jie; Zhang, Qiang; Sun, Zixuan; Wu, Xiaodan; Zhang, Xu; Zhu, Wei; Qian, Hui; Xu, Wenrong

2014-11-01

This study was designed to investigate the role of PDGF-DD secreted by gastric cancer-derived mesenchymal stem cells (GC-MSCs) in human gastric cancer progression. Gastric cancer cells were indirectly co-cultured with GC-MSCs in a transwell system. The growth and migration of gastric cancer cells were evaluated by cell colony formation assay and transwell migration assay, respectively. The production of PDGF-DD in GC-MSCs was determined by using Luminex and ELISA. Neutralization of PDGFR-β by su16f and siRNA interference of PDGF-DD in GC-MSCs was used to demonstrate the role of PDGF-DD produced by GC-MSCs in gastric cancer progression. GC-MSC conditioned medium promoted gastric cancer cell proliferation and migration in vitro and in vivo. Co-culture with GC-MSCs increased the phosphorylation of PDGFR-β in SGC-7901 cells. Neutralization of PDGFR-β by su16f blocked the promoting role of GC-MSC conditioned medium in gastric cancer cell proliferation and migration. Recombinant PDGF-DD duplicated the effects of GC-MSC conditioned medium on gastric cancer cells. Knockdown of PDGF-DD in GC-MSCs abolished its effects on gastric cancer cells in vitro and in vivo. PDGF-DD secreted by GC-MSCs is capable of promoting gastric cancer cell progression in vitro and in vivo. Targeting the PDGF-DD/PDGFR-β interaction between MSCs and gastric cancer cells may represent a novel strategy for gastric cancer therapy.

The CHOLEGAS study: multicentric randomized, blinded, controlled trial of gastrectomy plus prophylactic cholecystectomy versus gastrectomy only, in adults submitted to gastric cancer surgery with curative intent.

PubMed

Farsi, Marco; Bernini, Marco; Bencini, Lapo; Miranda, Egidio; Manetti, Roberto; de Manzoni, Giovanni; Verlato, Giuseppe; Marrelli, Daniele; Pedrazzani, Corrado; Roviello, Francesco; Marchet, Alberto; Cristadoro, Luigi; Gerard, Leonardo; Moretti, Renato

2009-05-15

The incidence of gallstones and gallbladder sludge is known to be higher in patients after gastrectomy than in general population. This higher incidence is probably related to surgical dissection of the vagus nerve branches and the anatomical gastrointestinal reconstruction. Therefore, some surgeons perform routine concomitant cholecystectomy during standard surgery for gastric malignancies. However, not all the patients who are diagnosed to have cholelithiasis after gastric cancer surgery will develop symptoms or require additional surgical treatments and a standard laparoscopic cholecystectomy is feasible even in those patients who underwent previous gastric surgery. At the present, no randomized study has been published and the decision of gallbladder management is left to each surgeon preference. The study is a randomized controlled investigation. The study will be performed in the General and Oncologic Surgery, Department of Oncology-Azienda Ospedaliero-Universitaria Careggi-Florence-Italy, a large teaching institution, with the participation of all surgeons who accept to be involved in, together with other Italian Surgical Centers, on behalf of the GIRCG (Italian Research Group for Gastric Cancer).The patients will be randomized into two groups: in the first group the patient will be submitted to prophylactic cholecystectomy during standard surgery for curable gastric cancer (subtotal or total gastrectomy), while in the second group he/she will be submitted to standard gastric surgery only. ClinicalTrials.gov ID. NCT00757640.

Tea polyphenols induce S phase arrest and apoptosis in gallbladder cancer cells

PubMed Central

Wang, Jiaqi; Pan, Yixuan; Hu, Jiacheng; Ma, Qiang; Xu, Yi; Zhang, Yijian; Zhang, Fei; Liu, Yingbin

2018-01-01

Gallbladder cancer (GBC) is the most common malignancy in the biliary tract. Without effective treatment, its prognosis is notoriously poor. Tea polyphenols (TPs) have many pharmacological and health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-thrombotic, antibacterial, and vasodilatory properties. However, the anti-cancer effect of TPs in human gallbladder cancer has not yet been determined. Cell viability and colony formation assay were used to investigate the cell growth. Cell cycle and apoptosis were evaluated by flow cytometry analysis. Western blot assay was used to detect the expression of proteins related to cell cycle and apoptosis. Human tumor xenografts were used to examine the effect of TPs on gallbladder cancer cells in vivo. TPs significantly inhibited cell growth of gallbladder cancer cell lines in a dose- and time-dependent manner. Cell cycle progression in GBC cells was blocked at the S phase by TPs. TPs also induced mitochondrial-related apoptosis in GBC cells by upregulating Bax, cleaved caspase-3, and cleaved PARP expressions and downregulating Bcl-2, cyclin A, and Cdk2 expressions. The effects of TPs on GBC were further proven in vivo in a mouse xenograft model. Our study is the first to report that TPs inhibit GBC cell growth and these compounds may have potential as novel therapeutic agents for treating gallbladder cancer. PMID:29513793

Hereditary Diffuse Gastric Cancer

MedlinePlus

... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...

Gallbladder cancer.

PubMed

Gourgiotis, Stavros; Kocher, Hemant M; Solaini, Leonardo; Yarollahi, Arvin; Tsiambas, Evangelos; Salemis, Nikolaos S

2008-08-01

Gallbladder cancer (GC) is a relatively rare but highly lethal neoplasm. We review the epidemiology, etiology, pathology, symptoms, diagnosis, staging, treatment, and prognosis of GC. A Pubmed database search between 1971 and February 2007 was performed. All abstracts were reviewed and articles with GC obtained; further references were extracted by hand-searching the bibliography. The database search was done in the English language. The accurate etiology of GC remains unclear, while the symptoms associated with primary GC are not specific. Treatment with radical cholecystectomy is curative but possible in only 10% to 30% of patients. For patients whose cancer is an incidental finding on pathologic review, re-resection is indicated, where feasible, for all disease except T1a. Patients with advanced disease should receive palliative treatment. Laparoscopic cholecystectomy is contraindicated in the presence of GC. Prognosis generally is extremely poor. Improvements in the outcome of surgical resection have caused this approach to be re-evaluated, while the role of chemotherapy and radiotherapy remains controversial.

[AFP-producing gastric cancer and hepatoid gastric cancer].

PubMed

Wang, Y K; Zhang, X T

2017-11-23

AFP-producing gastric cancer(AFPGC) and hepatoid adenocarcinoma of the stomach (HAS) are two special subtypes of gastric cancer. There are both correlation and difference between them. AFPGC is usually identified as primary gastric cancer with serum AFP level more than 20 ng/ml or showed AFP positive staining by immunohistochemistry. The diagnosis of HAS is mainly dependent on the pathological character of hepatocellular carcinoma-like differentiation of gastric cancer. The morbidity of AFPGC and HAS are rather low, especially the incidence of HAS is about 1%. The prognoses of these two subtypes are poorer than that of common gastric adenocarcinoma, due to a high incidence rate of liver metastasis and lymph node metastasis. With the development of next-generation sequencing and other genomic technologies, gastric cancers, including these two rare subtypes, are now being investigated in more detail at the molecular level. Treatment remains the biggest challenge, early diagnosis and radical resection can dramatically improve patients'prognosis. Monitoring serum AFP and abdominal imaging examination during follow-up is important for early detection of liver metastasis. In combination with local treatment methods such as transarterial chemoembolization and radiofrequency ablation of liver may further extend patients'survival time. Targeted therapy owes a great potential value in the future.

Selumetinib and Akt Inhibitor MK-2206 in Treating Patients With Refractory or Advanced Gallbladder or Bile Duct Cancer That Cannot Be Removed By Surgery

ClinicalTrials.gov

2014-09-08

Adenocarcinoma of the Gallbladder; Adenocarcinoma With Squamous Metaplasia of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage II Gallbladder Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer

Geographic variation of gallbladder cancer mortality and risk factors in Chile: a population-based ecologic study

PubMed Central

Andia, Marcelo E.; Hsing, Ann W.; Andreotti, Gabriella; Ferreccio, Catterina

2010-01-01

Chile’s gallbladder cancer rates are among the highest in the world, being the first cancer killer among Chilean women. To provide insights into the etiology of gallbladder cancer, we conducted an ecologic study examining the geographical variation of gallbladder cancer and several putative risk factors. The relative risk of dying from gallbladder cancer (relative to the national average mortality rate) between 1985 and 2003 was estimated for each of the 333 Chilean counties, using a hierarchical Poisson regression model, adjusting for age, sex, and geographical location. The risk of gallbladder cancer mortality was analyzed in relation to region (costal, inland, northern, and southern), poverty, Amerindian (Mapuche) population, typhoid fever, and access to cholecystectomy, using logistic regression analysis. There were 27,183 gallbladder cancer deaths, age-sex-adjusted county mortality rates ranging from 8.2 to 12.4 per 100,000 inhabitants, being higher in inland and southern regions; compare to the north-coastal, the northern-inland region had a 10-fold risk odds ratio (OR) (95% of confidence interval (95% CI): 2.4–42.2) and the southern-inland region had a 26-fold risk (OR 95%CI: 6.0–114.2). Independent risk factors for gallbladder cancer were: ethnicity (Mapuche) OR:3.9 (95%CI 1.8–8.7), typhoid fever OR:2.9 (95%CI 1.2–6.9), poverty OR:5.1 (95%CI 1.6–15.9), low access to cholecystectomy OR:3.9 (95%CI 1.5–10.1), low access to hospital care OR:14.2 (95%CI 4.2–48.7) and high urbanization OR:8.0 (95%CI 3.4–18.7). Our results suggest that gallbladder cancer in Chile may be related to both genetic factors and poor living conditions. Future analytic studies are needed to further clarify the role of these factors in gallbladder cancer etiology. PMID:18566990

Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery

ClinicalTrials.gov

2017-08-11

Adult Cholangiocarcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Hilar Cholangiocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma; Recurrent Childhood Liver Cancer; Recurrent Extrahepatic Bile Duct Carcinoma; Recurrent Gallbladder Carcinoma; Stage II Gallbladder Cancer; Stage III Childhood Hepatocellular Carcinoma; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IV Childhood Hepatocellular Carcinoma; Stage IV Distal Bile Duct Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Carcinoma

Biological Therapy in Treating Patients With Metastatic Cancer

ClinicalTrials.gov

2013-02-21

Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

Laparoscopic Radical Cholecystectomy for Primary or Incidental Early Gallbladder Cancer: The New Rules Governing the Treatment of Gallbladder Cancer

PubMed Central

Piozzi, Guglielmo Niccolò

2017-01-01

Aim To evaluate the technical feasibility and oncologic safety of laparoscopic radical cholecystectomy (LRC) for primary or incidental early gallbladder cancer (GBC) treatment. Methods Articles reporting LRC for GBC were reviewed from the first case reported in 2010 to 2015 (129 patients). 116 patients had a preoperative diagnosis of gallbladder cancer (primary GBC). 13 patients were incidental cases (IGBC) discovered during or after a laparoscopic cholecystectomy. Results The majority of patients who underwent LRC were pT2 (62.7% GBC and 63.6% IGBC). Parenchyma-sparing operation with wedge resection of the gallbladder bed or resection of segments IVb-V were performed principally. Laparoscopic lymphadenectomy was carried out according to the reported depth of neoplasm invasion. Lymph node retrieved ranged from 3 to 21. Some authors performed routine sampling biopsy of the inter-aorto-caval lymph nodes (16b1 station) before the radical treatment. No postoperative mortality was documented. Discharge mean day was POD 5th. 16 patients had post operative morbidities. Bile leakage was the most frequent post-operative complication. 5 y-survival rate ranged from 68.75 to 90.7 months. Conclusion Laparoscopy can not be considered as a dogmatic contraindication to GBC but a primary approach for early case (pT1b and pT2) treatment. PMID:28690639

Exposure to Mold Toxin Linked to Gallbladder Cancer Risk

Cancer.gov

A study by the National Cancer Institute reports an association between a marker of exposure to aflatoxin, a poisonous chemical produced by a type of mold, and gallbladder cancer in a population of men and women in Shanghai, China.

Trends in port-site metastasis after laparoscopic resection of incidental gallbladder cancer: A systematic review.

PubMed

Berger-Richardson, David; Chesney, Tyler R; Englesakis, Marina; Govindarajan, Anand; Cleary, Sean P; Swallow, Carol J

2017-03-01

The risk of port-site metastasis after laparoscopic removal of incidental gallbladder cancer was previously estimated to be 14-30%. The present study was designed to determine the incidence of port-site metastasis in incidental gallbladder cancer in the modern era (2000-2014) versus the historic era (1991-1999). We also investigated the site of port-site metastasis. Using PRISMA, a systematic review was conducted to identify papers that addressed the development of port-site metastasis after laparoscopic resection of incidental gallbladder cancer. Studies that described cancer-specific outcomes in ≥5 patients were included. A validated quality appraisal tool was used, and a weighted estimate of the incidence of port-site metastasis was calculated. Based on data extracted from 27 papers that met inclusion criteria, the incidence of port-site metastasis in incidental gallbladder cancer has decreased from 18.6% prior to 2000 (95% confidence interval 15.3-21.9%, n = 7) to 10.3% since then (95% confidence interval 7.9-12.7%, n = 20) (P < .001). The extraction site is at significantly higher risk than nonextraction sites. The incidence of port-site metastasis in incidental gallbladder cancer has decreased but remains high relative to other primary tumors. Any preoperative finding that raises the suspicion of gallbladder cancer should prompt further investigation and referral to a hepato-pancreato-biliary specialist. Copyright © 2016 Elsevier Inc. All rights reserved.

[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

Diagnosis and management of gallbladder polyps.

PubMed

Andrén-Sandberg, Ake

2012-05-01

Gallbladder cancer is a rather uncommon disease, when it gives symptoms it has usually reached an incurable stage. Therefore, every attempt must be made to find the asymptomatic stages and look for premalignant gallbladder polyps. Even if gallbladder cancer is a rare disease, gallbladder polyps are common, only a few polyps develop to cancer. This makes gallbladder polyps another problem: which are the polyps that must be surgically removed, which shall be followed-up, or for how long? The author used the keyword "gallbladder polypsn" in PubMed and reviewed the scientific literatures published from January 2000 to December 2011. The present review article has summarized almost all respects of gallbladder polyp, including the risk factors, clinical diagnosis and management, and comments made from the author, in which clinical treatments are recommended. It is author's purpose that the 11-year-knowledge about gallbladder polyps summarized from all worlds' literatures is enough to know how clinicians will handle the next patient with gallbladder polyp.

Diagnosis and Management of Gallbladder Polyps

PubMed Central

Andrén-Sandberg, Åke

2012-01-01

Gallbladder cancer is a rather uncommon disease, when it gives symptoms it has usually reached an incurable stage. Therefore, every attempt must be made to find the asymptomatic stages and look for premalignant gallbladder polyps. Even if gallbladder cancer is a rare disease, gallbladder polyps are common, only a few polyps develop to cancer. This makes gallbladder polyps another problem: which are the polyps that must be surgically removed, which shall be followed-up, or for how long? The author used the keyword “gallbladder polypsn” in PubMed and reviewed the scientific literatures published from January 2000 to December 2011. The present review article has summarized almost all respects of gallbladder polyp, including the risk factors, clinical diagnosis and management, and comments made from the author, in which clinical treatments are recommended. It is author's purpose that the 11-year-knowledge about gallbladder polyps summarized from all worlds’ literatures is enough to know how clinicians will handle the next patient with gallbladder polyp. PMID:22655278

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.

miR-125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer

PubMed Central

Yang, Dong; Zhan, Ming; Chen, Tao; Chen, Wei; Zhang, Yunhe; Xu, Sunwang; Yan, Jinchun; Huang, Qihong; Wang, Jian

2017-01-01

Gallbladder cancer represents the most common malignancy of the biliary tract and is highly lethal with less than 5% overall 5-year survival rate. Chemotherapy remains the major treatment for late-stage patients. However, insensitivity to these chemotherapeutic agents including cisplatin is common. MicroRNAs (miRNAs) have been shown as modulators of drug resistance in many cancer types. We used genome-wide gene expression analysis in clinical samples to identify miR-125b-5p down-regulated in gallbladder cancer. miR-125b-5p up-regulation promoted cell death in gallbladder cancer cells in the presence of cisplatin. In contrast, knockdown of miR-125b-5p reduced cell death in gallbladder cancer cells treated with cisplatin. Up-regulation of miR-125b-5p significantly decreased tumor growth in combination with cisplatin in a mouse model. We identified Bcl2 as a direct target of miR-125b-5p which mediates the function of miR-125b-5p in gallbladder cancer. In clinical samples, miR-125b-5p was down-regulated in gallbladder cancer whereas Bcl2 was up-regulated and their expression was inversely correlated. Moreover, low miR-125b-5p expression or high expression of Bcl2 is correlated with poor prognosis in gallbladder cancer. Taken together, our findings indicate that miR-125b-5p is a potent chemotherapy sensitizer and may function as a new biomarker for the prognosis of gallbladder cancer patients. PMID:28256505

The role of the gallbladder in humans.

PubMed

Turumin, J L; Shanturov, V A; Turumina, H E

2013-01-01

The basic function of the gallbladder in humans is one of protection. The accumulation of the primary bile acids (cholic acid and chenodeoxycholic acid) in the gallbladder reduces the formation of the secondary bile acids (deoxycholic acid and lithocholic acid), thus diminishing their concentration in the so-called gallbladder-independent enterohepatic circulation and protecting the liver, the stomach mucosa, the gallbladder, and the colon from their toxic hydrophobic effects. The presence or absence of the gallbladder in mammals is a determining factor in the synthesis of hydrophobic or hydrophilic bile acids. Because the gallbladder contracts 5-20 min after food is in the stomach and the "gastric chyme" moves from the stomach to the duodenum 1-3 h later, the function of the gallbladder bile in digestion may be insignificant. The aim of this article was to provide a detailed review of the role of the gallbladder and the mechanisms related to bile formation in humans. Copyright © 2012 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

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

Inflammatory metastatic breast cancer with gallbladder metastasis: an incidental finding.

PubMed

Ebrahim, Hassan; Graham, David; Rice, David; Ribadeneyra, Michael; Thorner, Kim; Shipley, William; Wehmueller, Michael

2015-07-01

Breast cancer is the most frequently diagnosed cancer in women, with an estimated 231,840 new cases representing 14.0% of all new cancer cases in the United States in 2015. Early screening and modern techniques of imaging and diagnosis have led to a significant improvement in detecting early-stage breast cancers and to a decrease in the incidence of metastatic breast cancer (MBC). About 20%-30% of patients who are initially diagnosed with an early-stage, nonmetastatic breast cancer will subsequently develop a distant metastatic disease. Between 6%-10% of the new breast cancer cases present initially as stage IV, referred to as de novo MBC. The most common sites of breast cancer metastases are lymph nodes, chest wall, skeleton, lung, skin, and the central nervous system (CNS). Lobular carcinoma, in particular, may metastasize to the gastrointestinal tract, peritoneum, and retroperitoneum. Gallbladder metastasis from breast cancer is very rare, and only 15-20 cases have been reported in the literature. Most of those cases have been associated particularly with a lobular histology. We report an additional rare case of MBC to the gallbladder, but with a ductal histology. ©2015 Frontline Medical Communications.

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

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

The risk of gallbladder cancer from polyps in a large multiethnic series.

PubMed

Aldouri, A Q; Malik, H Z; Waytt, J; Khan, S; Ranganathan, K; Kummaraganti, S; Hamilton, W; Dexter, S; Menon, K; Lodge, J P; Prasad, K R; Toogood, G J

2009-01-01

The aim of this study is assess whether patients with Indian ethnic background are at an increased risk of developing gallbladder cancer (GBC) if they have been diagnosed with ultrasonic abnormalities of the gallbladder. Between January 1998 and July 2006, 137,655 abdominal ultrasound examinations were performed in Leeds Teaching Hospitals NHS Trust. After the exclusion of repeat scans and those performed for renal or pelvic disease, 71,431 reports were included in this analysis. Patients in whom the diagnosis of GBC has been made without histology have been identified from the database of Northern and Yorkshire Cancer Registry and the presence of GBC was correlated with ultrasonic gallbladder abnormalities. Gallbladder polyps (GBP) were detected in 3.3% of patients and these were larger than 10 mm in 0.1% of the cases. Age above 60 years, Indian ethnic background, single GBP larger than 10mm, the presence of gallstones, severe gallbladder wall thickening and irregular thickening were independently associated with the higher odds of developing GBC. The prevalence of malignancy in those with GBP was significantly higher among patients with Indian ethnic background compared to Caucasian patients, 5.5% versus 0.08%, p<0.001. The presence of GBP, irrelevant of size, amongst patients of Indian ethnic decent, is an indication for further investigation and/or cholecystectomy.

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.

Usefulness of lavage cytology during endoscopic transpapillary catheterization into the gallbladder in the cytological diagnosis of gallbladder disease.

PubMed

Naito, Yoshiki; Okabe, Yoshinobu; Kawahara, Akihiko; Taira, Tomoki; Isida, Yusuke; Kaji, Ryouhei; Sata, Michio; Ureshino, Hiroki; Mikagi, Kazuhiro; Kinoshita, Hisafumi; Yasumoto, Makiko; Kusano, Hironori; Kage, Masayoshi; Yano, Hirohisa

2009-06-01

Many studies have reported methods of cell collection involving percutaneous transhepatic cholangiodrainage (PTCD) and fine-needle aspiration cytology for the diagnosis of gallbladder disease. However, few studies have described the use of a transpapillary approach, i.e., endoscopic transpapillary catheterization into the gallbladder (ETCG). In this study, we analyzed cells collected by ETCG to evaluate its usefulness in the cytological diagnosis of gallbladder disease. The subjects were 19 patients who had undergone ETCG for the diagnosis of gallbladder disease. Of these patients, 11 and 8 had gallbladder cancer and benign gallbladder disease, respectively. We also evaluated the diagnostic accuracy of PTCD cytology performed in 15 patients with gallbladder cancer.Specimens were cytologically diagnosed as normal or benign, indeterminate, suspected malignancy, malignant, and inadequate in 47% (9/19), 11% (2/19), 0% (0/19), 37% (7/19), and 5% (1/19) of patients, respectively. Specimens were diagnosed as malignant, indeterminate, normal or benign, and inadequate in 7, 2, 1, and 1, respectively, of the 11 patients diagnosed with gallbladder cancer. The sensitivity and specificity of ETCG cytology were 78 and 100%, respectively, whereas the diagnostic accuracy of PTCD cytology was 20% (3/15). None of the patients developed complications of ETCG. Despite its technical difficulty, ETCG for bile cytology allows the collection of adequate cell numbers from patients with benign disease or gallbladder cancer and facilitates a cytological diagnosis, making it a useful method for collecting cells. (c) 2009 Wiley-Liss, Inc.

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

Liver and gallbladder cancer in immigrants to Sweden.

PubMed

Hemminki, Kari; Mousavi, Seyed Mohsen; Brandt, Andreas; Ji, Jianguang; Sundquist, Jan

2010-03-01

The changes of cancer incidence upon immigration can be used as an estimator of environmental influence on cancer risk. We studied site-specific liver and biliary cancers in first-generation immigrants to Sweden with an aim to search for aetiological clues and to find evidence for indigenous incidence rates. We used the nation-wide Swedish Family-Cancer Database to calculate standardised incidence ratios (SIRs) in immigrants compared to native Swedes. A total of 1428 cancers were identified in immigrants whose median ages (years) at immigration were 27 for men and 26 for women and whose median diagnostic ages were 64 and 66, respectively. The highest SIRs of 6.7 for primary liver cancer were observed for men from East Asia and sub-Saharan Africa. Increased SIRs were recorded for male immigrants from previous Yugoslavia (1.78), Southern Europe (2.91), Turkey (2.15) and Asian Arab countries (2.89). For gallbladder cancer, only women from the Indian subcontinent (3.84) and Chile (2.34) had increased risk while some Northern European immigrants showed decreased risks. Primary liver cancer was increased in immigrants from endemic regions of hepatitis B virus infection but also from large regions lacking cancer incidence data, North Africa, Asian Arab countries, Turkey and previous Yugoslavia; these are probably intermediary risk regions for this infection. The consideration of these regions as risk areas would justify active diagnostic and vaccination programs. The increase in gallbladder cancer in Chileans and Indians suggests that some persistent damage was inflicted before emigration, characterisation of which will be a challenge for aetiological studies. Copyright 2009 Elsevier Ltd. All rights reserved.

Clinical epidemiology of gastric cancer in Hehuang valley of China: A 10-year epidemiological study of gastric cancer

PubMed Central

Yan, Su; Li, Bin; Bai, Zhen-Zhong; Wu, Jun-Qi; Xie, Da-Wei; Ma, Ying-Cai; Ma, Xu-Xiang; Zhao, Jun-Hui; Guo, Xin-Jian

2014-01-01

AIM: To investigate the clinical epidemiological characteristics of gastric cancer in the Hehuang valley, China, to provide a reference for treatment and prevention of regional gastric cancer. METHODS: Between February 2003 and February 2013, the records of 2419 patients with gastric cancer were included in this study. The patient’s characteristics, histological and pathological features, as well as the dietary habits of the patients, were investigated. RESULTS: The clinical data showed that adenocarcinoma was the leading histological type of gastric cancer in this area. Characteristics of gastric cancer in different ethnic groups and age showed that the 60.55-65.50 years group showed the high incidence of gastric cancer in all ethnic groups. There were more male gastric cancer patients than female. Intestinal was the most common type of gastric cancer in the Hehuang valley. There was no significant difference in the proportion of sex in terms of Helicobacter pylori infection. The impact of dietary habits on gastric cancer showed that regular consumption of fried or grilled food, consumption of high-salt, high-fat and spicy food and drinking strong Boiled brick-tea were three important factors associated with gastric cancer in males and females. CONCLUSION: Differences existed in race, sex, and age of patients according to the epidemiology of gastric cancer in the Hehuang valley. Moreover, dietary habits was also an important factor contributing to gastric cancer. PMID:25132766

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

Gallbladder Cancer Presenting with Jaundice: Uniformly Fatal or Still Potentially Curable?

PubMed

Tran, Thuy B; Norton, Jeffrey A; Ethun, Cecilia G; Pawlik, Timothy M; Buettner, Stefan; Schmidt, Carl; Beal, Eliza W; Hawkins, William G; Fields, Ryan C; Krasnick, Bradley A; Weber, Sharon M; Salem, Ahmed; Martin, Robert C G; Scoggins, Charles R; Shen, Perry; Mogal, Harveshp D; Idrees, Kamran; Isom, Chelsea A; Hatzaras, Ioannis; Shenoy, Rivfka; Maithel, Shishir K; Poultsides, George A

2017-08-01

Jaundice as a presenting symptom of gallbladder cancer has traditionally been considered to be a sign of advanced disease, inoperability, and poor outcome. However, recent studies have demonstrated that a small subset of these patients can undergo resection with curative intent. Patients with gallbladder cancer managed surgically from 2000 to 2014 in 10 US academic institutions were stratified based on the presence of jaundice at presentation (defined as bilirubin ≥4 mg/ml or requiring preoperative biliary drainage). Perioperative morbidity, mortality, and overall survival were compared between jaundiced and non-jaundiced patients. Of 400 gallbladder cancer patients with available preoperative data, 108 (27%) presented with jaundice while 292 (73%) did not. The fraction of patients who eventually underwent curative-intent resection was much lower in the presence of jaundice (n = 33, 30%) than not (n = 218, 75%; P < 0.001). Jaundiced patients experienced higher perioperative morbidity (69 vs. 38%; P = 0.002), including a much higher need for reoperation (12 vs. 1%; P = 0.003). However, 90-day mortality (6.5 vs. 3.6%; P = 0.35) was not significantly higher. Overall survival after resection was worse in jaundiced patients (median 14 vs. 32 months; P < 0.001). Further subgroup analysis within the jaundiced patients revealed a more favorable survival after resection in the presence of low CA19-9 < 50 (median 40 vs. 12 months; P = 0.003) and in the absence of lymphovascular invasion (40 vs. 14 months; P = 0.014). Jaundice is a powerful preoperative clinical sign of inoperability and poor outcome among gallbladder cancer patients. However, some of these patients may still achieve long-term survival after resection, especially when preoperative CA19-9 levels are low and no lymphovascular invasion is noted pathologically.

Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

ClinicalTrials.gov

2018-03-08

Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer

Outcome of gallbladder preservation in surgical management of primary bile duct stones.

PubMed

Tian, Ming-Guo; Shi, Wei-Jin; Wen, Xin-Yuan; Yu, Hai-Wen; Huo, Jing-Shan; Zhou, Dong-Feng

2003-08-01

To evaluate the methods and outcome of gallbladder preservation in surgical treatment of primary bile duct stones. Thirty-five patients with primary bile duct stones and intact gallbladders received stone extraction by two operative approaches, 23 done through the intrahepatic duct stump (RBD-IDS, the RBD-IDS group) after partial hepatectomy and 12 through the hepatic parenchyma by retrograde puncture (RBD-RP, the RBD-RP group). The gallbladders were preserved and the common bile duct (CBD) incisions were primarily closed. The patients were examined postoperatively by direct cholangiography and followed up by ultrasonography once every six months. In the RBD-IDS group, residual bile duct stones were found in three patients, which were cleared by a combination of fibrocholedochoscopic extraction and lithotripsy through the drainage tracts. The tubes were removed on postoperative day 22 (range: 16-42 days). In the RBD-RP group, one patient developed hemobilia and was cured by conservative therapy. The tubes were removed on postoperative day 8 (range: 7-11 days). Postoperative cholangiography showed that all the gallbladders were well opacified, contractile and smooth. During 54 (range: 6-120 months) months of follow-up, six patients had mildly thickened cholecystic walls without related symptoms and further changes, two underwent laparotomies because of adhesive intestinal obstruction and gastric cancer respectively, three died of cardiopulmonary diseases. No stones were found in all the preserved gallbladders. The intact gallbladders preserved after surgical extraction of primary bile duct stones will not develop gallstones. Retrograde biliary drainage is an optimal approach for gallbladder preservation.

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.

RNA sequencing-based analysis of gallbladder cancer reveals the importance of the liver X receptor and lipid metabolism in gallbladder cancer

PubMed Central

Zuo, Mingxin; Rashid, Asif; Wang, Ying; Jain, Apurva; Li, Donghui; Behari, Anu; Kapoor, Vinay Kumar; Koay, Eugene J.; Chang, Ping; Vauthey, Jean Nicholas; Li, Yanan; Espinoza, Jaime A.; Roa, Juan Carlos; Javle, Milind

2016-01-01

Gallbladder cancer (GBC) is an aggressive malignancy. Although surgical resection may be curable, most patients are diagnosed at an advanced unresectable disease stage. Cholelithiasis is the major risk factor; however the pathogenesis of the disease, from gallstone cholecystitis to cancer, is still not understood. To understand the molecular genetic underpinnings of this cancer and explore novel therapeutic targets for GBC, we examined the key genes and pathways involved in GBC using RNA sequencing. We performed gene expression analysis of 32 cases of surgically-resected GBC along with normal gallbladder tissue controls. We observed that 519 genes were differentially expressed between GBC and normal GB mucosal controls. The liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor (FXR) /RXR pathways were the top canonical pathways involved in GBC. Key genes in these pathways, including SERPINB3 and KLK1, were overexpressed in GBC, especially in female GBC patients. Additionally, ApoA1 gene expression suppressed in GBC as compared with normal control tissues. LXR and FXR genes, known to be important in lipid metabolism also function as tumor suppressors and their down regulation appears to be critical for GBC pathogenesis. LXR agonists may have therapeutic value and as potential therapeutic targets. PMID:27167107

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

Are histological alterations observed in the gallbladder precancerous lesions?

PubMed Central

Meirelles-Costa, Adriana Lúcia Agnelli; Bresciani, Claudio José Caldas; Perez, Rodrigo Oliva; Bresciani, Barbara Helou; Siqueira, Sheila Aparecida C.; Cecconello, Ivan

2010-01-01

INTRODUCTION Gallbladder cancer, which is characterized by rapid progression and a poor prognosis, is a complex disease to treat. Unfortunately, little is known currently about its etiology or pathogenesis. A better understanding of its carcinogenesis and determining risk factors that lead to its development could help improve the available treatment options. METHOD Based on this better understanding, the histological alterations (such as acute cholecystitis, adenomyomatosis, xanthogranulomatous cholecystitis, polyps, pyloric metaplasia, intestinal metaplasia, dysplasia, cancer and others) in gallbladders from 1,689 patients who underwent laparoscopic cholecystectomy for cholecystolithiasis were analyzed. The association of these gallbladder histological alterations with clinical data was studied. RESULTS Gender analysis revealed a greater incidence of inflammatory changes in males, while dysplasia and cancer were only found in women. The incidence of cholesterolosis was greater in the patients 60 years of age and under, and the incidence of adenomyomatosis and gangrene was greater in the elderly patients. A progressive increase in the average age was observed as alterations progressed through pyloric metaplasia, intestinal metaplasia, dysplasia and then cancer, suggesting that the metaplasia-dysplasia-carcinoma sequence may occur in gallbladder cancer. Gallbladder histological alterations were also observed in asymptomatic patients. CONCLUSION The results of this study suggest that there could be an association between some histological alterations of gallbladder and cancer, and they also suggest that the metaplasia-dysplasia-carcinoma sequence could in fact be true in the case of gallbladder cancer. Nevertheless, further studies directed towards a perfect understanding of gallbladder carcinogenesis are required. PMID:20186297

Subtotal gastrectomy for gastric cancer

PubMed Central

Santoro, Roberto; Ettorre, Giuseppe Maria; Santoro, Eugenio

2014-01-01

Although a steady decline in the incidence and mortality rates of gastric carcinoma has been observed in the last century worldwide, the absolute number of new cases/year is increasing because of the aging of the population. So far, surgical resection with curative intent has been the only treatment providing hope for cure; therefore, gastric cancer surgery has become a specialized field in digestive surgery. Gastrectomy with lymph node (LN) dissection for cancer patients remains a challenging procedure which requires skilled, well-trained surgeons who are very familiar with the fast-evolving oncological principles of gastric cancer surgery. As a matter of fact, the extent of gastric resection and LN dissection depends on the size of the disease and gastric cancer surgery has become a patient and “disease-tailored” surgery, ranging from endoscopic resection to laparoscopic assisted gastrectomy and conventional extended multivisceral resections. LN metastases are the most important prognostic factor in patients that undergo curative resection. LN dissection remains the most challenging part of the operation due to the location of LN stations around major retroperitoneal vessels and adjacent organs, which are not routinely included in the resected specimen and need to be preserved in order to avoid dangerous intra- and postoperative complications. Hence, the surgeon is the most important non-TMN prognostic factor in gastric cancer. Subtotal gastrectomy is the treatment of choice for middle and distal-third gastric cancer as it provides similar survival rates and better functional outcome compared to total gastrectomy, especially in early-stage disease with favorable prognosis. Nonetheless, the resection range for middle-third gastric cancer cases and the extent of LN dissection at early stages remains controversial. Due to the necessity of a more extended procedure at advanced stages and the trend for more conservative treatments in early gastric cancer, the

Promoter methylation profile in gallbladder cancer.

PubMed

Roa, Juan Carlos; Anabalón, Leonardo; Roa, Iván; Melo, Angélica; Araya, Juan Carlos; Tapia, Oscar; de Aretxabala, Xavier; Muñoz, Sergio; Schneider, Barbara

2006-03-01

Methylation in the promoter region of genes is an important mechanism of inactivation of tumor suppressor genes. Our objective was to analyze the methylation pattern of some of the genes involved in carcinogenesis of the gallbladder, examining the immunohistochemical expression of proteins, clinical features, and patient survival time. Twenty cases of gallbladder cancer were selected from the frozen tumor bank. The DNA extracted was analyzed by means of a methylation-specific polymerase chain reaction test for the CDKN2A (p16), MLH1, APC, FHIT, and CDH1 (E-cadherin) genes. Morphological and clinical data and follow-up information were obtained. All cases were in an advanced stage: histologically moderate or poorly differentiated tumors (95%). Methylation of the promoter area of genes was observed in 5%, 20%, 30%, 40%, and 65% of cases, and an altered immunohistochemical pattern (AIP) in 5%, 35%, 21%, 25%, and 66% for the MLH1, CDKN2A, FHIT, APC, and CDH1 genes, respectively. The Kappa concordance index between methylation of the promoter area and AIP for the MLH1 and CDH1 genes was very high (K > 0.75) and substantial for APC (K > 0.45). No correlation was found between survival time and the methylation of the genes studied. The high frequency of gene methylation (with the exception of MLH1) and the high agreement between AIP and methylation of the gene promoter area for the MLH1, APC, and CDH1 genes suggest that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis.

Metagenomics of Microbial Communities in Gallbladder Bile from Patients with Gallbladder Cancer or Cholelithiasis

PubMed

Tsuchiya, Yasuo; Loza, Ernest; Villa-Gomez, Guido; Trujillo, Carlos C; Baez, Sergio; Asai, Takao; Ikoma, Toshikazu; Endoh, Kazuo; Nakamura, Kazutoshi

2018-04-25

Salmonella typhi and Helicobacter infections have been shown to increase risk of gallbladder cancer (GBC), but findings have been inconsistent. Other bacterial infections may also be associated with GBC. However, information on microbial pathogens in gallbladder bile of GBC patients is scarce. We aimed to investigate the microbial communities in gallbladder bile of patients with GBC and cholelithiasis (CL). Seven GBC patients and 30 CL patients were enrolled in this study. Genomic DNA was extracted from bile and the V3-V4 region of 16S rRNA was amplified. The sequencing results were compared with the 16S database, and the bacteria were identified by homology searches and phylogenetic analysis. DNA was detected in the bile of three GBC (42.9%; Bolivia, 1; Chile, 2) and four CL patients (13.3%; Bolivia, 1; Chile, 3). Of the 37 patients, 30 (81.1%) were negative and unable to analyze. Salmonella typhi and Helicobacter sp. were not detected in bile from any GBC patients. As the predominant species, Fusobacterium nucleatum, Escherichia coli, and Enetrobacter sp. were detected in bile from GBC patients. Those in bile from CL patients were Escherichia coli, Salmonella sp., and Enerococcus gallinarum. Escherichia coli was detected in bile samples from both GBC and CL patients. Whether the bacteria detected in bile from GBC patients would associated with the development of GBC warrant further investigation. Creative Commons Attribution License

Nomogram for Predicting the Benefit of Adjuvant Chemoradiotherapy for Resected Gallbladder Cancer

PubMed Central

Wang, Samuel J.; Lemieux, Andrew; Kalpathy-Cramer, Jayashree; Ord, Celine B.; Walker, Gary V.; Fuller, C. David; Kim, Jong-Sung; Thomas, Charles R.

2011-01-01

Purpose Although adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of this disease. The specific aim of this study was to create a decision aid to help make individualized estimates of the potential survival benefit of adjuvant chemoradiotherapy for patients with resected gallbladder cancer. Methods Patients with resected gallbladder cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) –Medicare database who were diagnosed between 1995 and 2005. Covariates included age, race, sex, stage, and receipt of adjuvant chemotherapy or chemoradiotherapy (CRT). Propensity score weighting was used to balance covariates between treated and untreated groups. Several types of multivariate survival regression models were constructed and compared, including Cox proportional hazards, Weibull, exponential, log-logistic, and lognormal models. Model performance was compared using the Akaike information criterion. The primary end point was overall survival with or without adjuvant chemotherapy or CRT. Results A total of 1,137 patients met the inclusion criteria for the study. The lognormal survival model showed the best performance. A Web browser–based nomogram was built from this model to make individualized estimates of survival. The model predicts that certain subsets of patients with at least T2 or N1 disease will gain a survival benefit from adjuvant CRT, and the magnitude of benefit for an individual patient can vary. Conclusion A nomogram built from a parametric survival model from the SEER-Medicare database can be used as a decision aid to predict which gallbladder patients may benefit from adjuvant CRT. PMID:22067404

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.

Endoscopic gastric atrophy is strongly associated with gastric cancer development after Helicobacter pylori eradication.

PubMed

Toyoshima, Osamu; Yamaji, Yutaka; Yoshida, Shuntaro; Matsumoto, Shuhei; Yamashita, Hiroharu; Kanazawa, Takamitsu; Hata, Keisuke

2017-05-01

Risk factors for gastric cancer during continuous infection with Helicobacter pylori have been well documented; however, little has been reported on the risk factors for primary gastric cancer after H. pylori eradication. We conducted a retrospective, endoscopy-based, long-term, large-cohort study to clarify the risk factors for gastric cancer following H. pylori eradication. Patients who achieved successful H. pylori eradication and periodically underwent esophagogastroduodenoscopy surveillance thereafter at Toyoshima Endoscopy Clinic were enrolled. The primary endpoint was the development of gastric cancer. Statistical analysis was performed using the Kaplan-Meier method and Cox's proportional hazards models. Gastric cancer developed in 15 of 1232 patients. The cumulative incidence rates were 1.0 % at 2 years, 2.6 % at 5 years, and 6.8 % at 10 years. Histology showed that all gastric cancers (17 lesions) in the 15 patients were of the intestinal type, within the mucosal layer, and <20 mm in diameter. Based on univariate analysis, older age and higher endoscopic grade of gastric atrophy were significantly associated with gastric cancer development after eradication of H. pylori, and gastric ulcers were marginally associated. Multivariate analysis identified higher grade of gastric atrophy (hazard ratio 1.77; 95 % confidence interval 1.12-2.78; P = 0.01) as the only independently associated parameter. Endoscopic gastric atrophy is a major risk factor for gastric cancer development after H. pylori eradication. Further long-term studies are required to determine whether H. pylori eradication leads to regression of H. pylori-related gastritis and reduces the risk of gastric cancer.

Implications of the Index Cholecystectomy and Timing of Referral for Radical Resection of Advanced Incidental Gallbladder Cancer

PubMed Central

Ausania, F; White, SA; French, JJ; Jaques, BC; Charnley, RM; Manas, DM

2015-01-01

Introduction Advanced (pT2/T3) incidental gallbladder cancer is often deemed unresectable after restaging. This study assesses the impact of the primary operation, tumour characteristics and timing of management on re-resection. Methods The records of 60 consecutive referrals for incidental gallbladder cancer in a single tertiary centre from 2003 to 2011 were reviewed retrospectively. Decision on re-resection of incidental gallbladder cancer was based on delayed interval restaging at three months following cholecystectomy. Demographics, index cholecystectomy data, primary pathology, CA19–9 tumour marker levels at referral and time from cholecystectomy to referral as well as from referral to restaging were analysed. Results Thirty-seven patients with pT2 and twelve patients with pT3 incidental gallbladder cancer were candidates for radical re-resection. Following interval restaging, 24 patients (49%) underwent radical resection and 25 (51%) were deemed inoperable. The inoperable group had significantly more patients with positive resection margins at cholecystectomy (p=0.002), significantly higher median CA19–9 levels at referral (p=0.018) and were referred significantly earlier (p=0.004) than the patients who had resectable tumours. On multivariate analysis, urgent referral (p=0.036) and incomplete cholecystectomy (p=0.048) were associated significantly with inoperable disease following restaging. Conclusions In patients with incidental, potentially resectable, pT2/T3 gallbladder cancer, inappropriate index cholecystectomy may have a significant impact on tumour dissemination. Early referral of breached tumours is not associated with resectability. PMID:25723690

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.

[Application of pylorus-vagus-preserving gastrectomy in early gastric cancer in middle third of stomach].

PubMed

Hu, Junfeng; Shao, Qinshu; Sun, Yuanshui; Xu, Xiaodong; Xu, Ji

2015-04-14

To evaluate the long-term outcomes of pylorus-vagus-preserving partial gastrectomy for early gastric cancer in middle third of stomach. Between January 2004 and June 2009, 46 patients with early gastric cancer in middle third of stomach underwent pylorus-vagus-preserving partial gastrectomy (PPG) while another 85 patients had conventional distal gastrectomy (DG). Clinicopathologic data and follow-up results of two groups were analyzed retrospectively, including the results of subjective nutritional assessments, laboratory blood biochemical data, endoscopic findings of remnant stomach and total 5-year survival rates. Postprandial dumping syndrome occurred in 7 patients (8.2%) in DG group while no syndrome occurred in PPG group. The incidence of gallbladder stones at 18 months after operation in DG group was higher than that in PPG group. Significant difference existed between two groups (P<0.05). Even though no significant difference existed in laboratory blood biochemical data and endoscopic findings, PPG group recovered better and regurgitation was frequently found in DG group. Food residue in gastric remnant was frequently observed in PPG (31.1%) than in DG (10.8%, P<0.05) by endoscopic findings. At 2 years post-operation, the postoperative 5-year recurrence rate was 6.5% (2/46) in PPG group versus 8.2% (7/85) in DG group. However no significant difference existed between 2 groups (P=0.724). No significant difference existed between PPG group (91.3%) and DG group (90.6%) in overall 5-year survival rate. For early gastric cancer in middle third of stomach, pylorus-vagus-preserving partial gastrectomy is effective in maintaining postoperative function. And it has the same postoperative survival rate as conventional distal gastrectomy.

Comparison of clinical outcomes of incidental and non- incidental gallbladder cancers: a single-center cross- sectional study.

PubMed

Cha, Byung Hyo; Bae, Jong-Myun

2014-01-01

Gallbladder cancer (GBC) is a rare malignancy characterized by high invasiveness and poor survival. In a nation-wide cancer survey, the age-standardized incidence rate of GBC was the highest in Jeju Island compared to 15 other provinces in Korea. The purpose of this study was to compare the clinical outcomes of GBC according to the nature of diagnosis, that is, incidental versus non-incidental. Consecutive patients who were newly diagnosed with GBC at the Digestive Disease Center and Department of Internal Medicine, Cheju Halla General Hospital, between November 2008 and November 2011, were enrolled and divided into 2 groups: incidental gallbladder cancer (IGBC) and non-incidental gallbladder cancer (NIGBC). Clinical outcomes were retrospectively compared between the two groups. Seventy-nine patients were enrolled and analyzed in our study. Thirty-three (41.8%) and 46 (58.2%) were identified as IGBC and NIGBC, respectively. The proportions of patients with gallstone disease, gallbladder polyp, and cholecystectomy were significantly different between the two groups. Additionally, the median survival rate was significantly higher for patients with IGBC than for those with NIGBC (11.4, 95% confidence interval, 5.6-13.7 vs 4.0, 95% confidence interval 3.03-5.96 months; p=0.01) during a median follow-up period of 5.7 months. Patients with IGBC showed better clinical prognosis than those with NIGBC. Therefore, patients with gallstone disease or gallbladder polyps, major predictive risk factors for IGBC, should undergo advanced work-up for chelecystectomy.

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

Integrated Cancer Repository for Cancer Research

ClinicalTrials.gov

2017-05-05

Pancreatic Cancer; Thyroid Cancer; Lung Cancer; Esophageal Cancer; Thymus Cancer; Colon Cancer; Rectal Cancer; GIST; Anal Cancer; Bile Duct Cancer; Duodenal Cancer; Gallbladder Cancer; Gastric Cancer; Liver Cancer; Small Intestine Cancer; Peritoneal Surface Malignancies; Familial Adenomatous Polyposis; Lynch Syndrome; Bladder Cancer; Kidney Cancer; Penile Cancer; Prostate Cancer; Testicular Cancer; Ureter Cancer; Urethral Cancer; Hypopharyngeal Cancer; Laryngeal Cancer; Lip Cancer; Oral Cavity Cancer; Nasopharyngeal Cancer; Oropharyngeal Cancer; Paranasal Sinus Cancer; Nasal Cavity Cancer; Salivary Gland Cancer; Skin Cancer; CNS Tumor; CNS Cancer; Mesothelioma; Breastcancer; Leukemia; Melanoma; Sarcoma; Unknown Primary Tumor; Multiple Myeloma; Ovarian Cancer; Endometrial Cancer; Vaginal Cancer

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 ...

Sweetened Beverage Consumption and Risk of Biliary Tract and Gallbladder Cancer in a Prospective Study.

PubMed

Larsson, Susanna C; Giovannucci, Edward L; Wolk, Alicja

2016-10-01

Sugar-sweetened beverage consumption raises blood glucose concentration and has been positively associated with weight gain and type 2 diabetes, all of which have been implicated in the development of biliary tract cancer (BTC). This study examined the hypothesis that sweetened beverage consumption is positively associated with risk of BTC in a prospective study. The study population comprised 70 832 Swedish adults (55.9% men, age 45-83 years) from the Swedish Mammography Cohort and Cohort of Swedish Men who were free of cancer and diabetes and completed a food frequency questionnaire at baseline. Incident BTC case patients were ascertained through linkage with the Swedish Cancer Register. Cox proportional hazards regression model was used to analyze the data. All statistical tests were two-sided. During a mean follow-up of 13.4 years, 127 extrahepatic BTC case patients (including 71 gallbladder cancers) and 21 intrahepatic BTC case patients were ascertained. After adjustment for other risk factors, women and men in the highest category of combined sugar-sweetened and artificially sweetened beverage consumption had a statistically significantly increased risk of extrahepatic BTC and gallbladder cancer. The multivariable hazard ratios for two or more servings per day (200 mL/serving) of sweetened beverages compared with no consumption were 1.79 (95% confidence interval [CI] = 1.02 to 3.13) for extrahepatic BTC and 2.24 (95% CI = 1.02 to 4.89) for gallbladder cancer. The corresponding hazard ratio for intrahepatic BTC was 1.69 (95% CI = 0.41 to 7.03). These findings support the hypothesis that high consumption of sweetened beverages may increase the risk of BTC, particularly gallbladder cancer. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

An Aggressive Surgical Approach Leads to Improved Survival in Patients With Gallbladder Cancer

PubMed Central

Dixon, Elijah; Vollmer, Charles M.; Sahajpal, Ajay; Cattral, Mark; Grant, David; Doig, Christopher; Hemming, Al; Taylor, Bryce; Langer, Bernard; Greig, Paul; Gallinger, Steven

2005-01-01

Objective: To determine if an aggressive surgical approach, with an increase in R0 resections, has resulted in improved survival for patients with gallbladder cancer. Summary Background Data: Many physicians express a relatively nihilistic approach to the treatment of gallbladder cancer; consensus among surgeons regarding the indications for a radical surgical approach has not been reached. Methods: A retrospective review of all patients with gallbladder cancer admitted during the past 12 years was conducted. Ninety-nine patients were identified. Cases treated during the 12-year period 1990 to 2002 were divided into 2 time-period (TP) cohorts, those treated in the first 6 years (TP1, N = 35) and those treated in the last 6 years (TP2, N = 64). Results: Disease stratification by stage and other demographic features were similar in the 2 time periods. An operation with curative intent was performed on 38 patients. Nine (26%) R0 resections were performed in TP1 and 24 (38%) in TP2. The number of liver resections, as well as the frequency of extrahepatic biliary resections, was greater in TP2 (P < 0.04). In both time periods, an R0 resection was associated with improved survival (P < 0.02 TP1, P < 0.0001 TP2). Overall survival of all patients in TP2 was significantly greater than in TP1 (P < 0.03), with a median survival of 9 months in TP1 and 17 months in TP2. The median 5-year survival in TP1 was 7%, and 35% in TP2. The surgical mortality rate for the entire cohort was 2%, with a 49% morbidity rate. Conclusions: A margin-negative, R0 resection leads to improved survival in patients with gallbladder cancer. PMID:15729060

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

Gallbladder stones and gallbladder polyps associated with increased risk of colorectal adenoma in men.

PubMed

Liu, Yen-Ling; Wu, Jin-Shang; Yang, Yi-Ching; Lu, Feng-Hwa; Lee, Chih-Ting; Lin, Wan-Ju; Chang, Chih-Jen

2018-04-01

Most cases of colorectal cancer develop via an adenoma to carcinoma sequence. Gallbladder polyps share some risk factors with colorectal polyps. Little is known about the relationship between gallbladder diseases and different status of colorectal polyps by gender. This study was to investigate the association of gallbladder stones and polyps with colorectal adenomas by gender in a Taiwanese population. A total of 7066 eligible subjects who underwent a total colonoscopy as a part of health check-up between January 2001 and August 2009 were recruited. Colonoscopic findings were classified into polyp-free, non-neoplastic polyps and colorectal adenomas. Gallbladder stones and gallbladder polyps were diagnosed based on ultrasonographic findings. There was a significant difference in the status of colon polyps between subjects with and without gallbladder polyps. However, the status of colon polyps was not significantly different between subjects with or without gallbladder stones. After adjusting obesity, fasting plasma glucose, and other variables, there was a positive relationship between gallbladder polyps and colorectal adenomas (odds ratio [OR]: 1.396, 95% confidence interval [CI]: 1.115-1.747) but not non-neoplastic polyps in all subjects. In men, gallbladder polyps (OR: 1.560, 95% CI: 1.204-2.019) and gallbladder stones (OR: 1.465, 95% CI 1.081-1.984) were positively associated with colorectal adenomas. In women, neither gallbladder polyps nor gallbladder stones were significantly related to colon polyps. Both gallbladder polyps and gallbladder stones were associated with an increased risk of colorectal adenomas in men but not in women. Gender difference was significant for the association between gallbladder lesions and colorectal polyps. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

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.

EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-01-15

Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

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.

Inflammatory fibroid polyp of the gallbladder bearing a platelet-derived growth factor receptor alpha mutation.

PubMed

Martini, Maurizio; Santoro, Luisa; Familiari, Pietro; Costamagna, Guido; Ricci, Riccardo

2013-05-01

The inflammatory fibroid polyp (IFP) is a benign lesion occurring in the digestive tract, mostly in the stomach and small bowel, composed of fibrovascular tissue infiltrated by inflammatory cells including eosinophils and mastocytes. Its pathogenesis has been controversial (reactive versus neoplastic). The recent finding of mutations in platelet-derived growth factor receptor α (PDGFRA) in most gastric and small intestinal IFPs supported their neoplastic etiology, moreover helping in their differential diagnosis. In the only gallbladder IFP reported so far, the diagnosis was based on morphologic and immunohistochemical grounds, which in current standards would probably be considered not fully conclusive. Conversely, the gallbladder IFP we report shows typical pathologic features supported by a PDGFRA mutation, similar to its usual gastric and small intestinal counterparts, constituting the first report of an unequivocal IFP at gallbladder level. Thus, IFPs must be considered in the differential diagnosis of gallbladder mesenchymal masses, and genetic analysis of PDGFRA is a helpful tool for this purpose.

Body Size Indicators and Risk of Gallbladder Cancer: Pooled Analysis of Individual-Level Data from 19 Prospective Cohort Studies.

PubMed

Campbell, Peter T; Newton, Christina C; Kitahara, Cari M; Patel, Alpa V; Hartge, Patricia; Koshiol, Jill; McGlynn, Katherine A; Adami, Hans-Olov; Berrington de González, Amy; Beane Freeman, Laura E; Bernstein, Leslie; Buring, Julie E; Freedman, Neal D; Gao, Yu-Tang; Giles, Graham G; Gunter, Marc J; Jenab, Mazda; Liao, Linda M; Milne, Roger L; Robien, Kim; Sandler, Dale P; Schairer, Catherine; Sesso, Howard D; Shu, Xiao-Ou; Weiderpass, Elisabete; Wolk, Alicja; Xiang, Yong-Bing; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Gapstur, Susan M

2017-04-01

Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size measures is lacking. Methods: Associations of adult BMI, young adult BMI, height, adult weight gain, waist circumference (WC), waist-height ratio (WHtR), hip circumference (HC), and waist-hip ratio (WHR) with gallbladder cancer risk were evaluated. Individual-level data from 1,878,801 participants in 19 prospective cohort studies (14 studies had circumference measures) were harmonized and included in this analysis. Multivariable Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI). Results: After enrollment, 567 gallbladder cancer cases were identified during 20.1 million person-years of observation, including 361 cases with WC measures. Higher adult BMI (per 5 kg/m 2 , HR: 1.24; 95% CI, 1.13-1.35), young adult BMI (per 5 kg/m 2 , HR: 1.12; 95% CI, 1.00-1.26), adult weight gain (per 5 kg, HR: 1.07; 95% CI, 1.02-1.12), height (per 5 cm, HR: 1.10; 95% CI, 1.03-1.17), WC (per 5 cm, HR: 1.09; 95% CI, 1.02-1.17), WHtR (per 0.1 unit, HR: 1.24; 95% CI, 1.00-1.54), and HC (per 5 cm, HR: 1.13; 95% CI, 1.04-1.22), but not WHR (per 0.1 unit, HR: 1.03; 95% CI, 0.87-1.22), were associated with higher risks of gallbladder cancer, and results did not differ meaningfully by sex or other demographic/lifestyle factors. Conclusions: These findings indicate that measures of overall and central excess body weight are associated with higher gallbladder cancer risks. Impact: Excess body weight is an important, and potentially preventable, gallbladder cancer risk factor. Cancer Epidemiol Biomarkers Prev; 26(4); 597-606. ©2017 AACR . ©2017 American Association for Cancer Research.

Epigenetic regulation in gallbladder cancer: Promoter methylation profiling as emergent novel biomarkers.

PubMed

Tekcham, Dinesh Singh; Tiwari, Pramod Kumar

2016-12-01

DNA methylation, once considered to rule the sex determination in Mary Lyon's hypothesis, has now reached the epicenter of human diseases, from monogenic (e.g. Prader Willi syndrome, Angelman syndromes and Beckwith-Wiedemann syndrome) to polygenic diseases, like cancer. Technological developments from gold standard to high throughput technologies have made tremendous advancement to define the epigenetic mechanism of cancer. Gallbladder cancer (GBC) is a fatal health issue affecting mostly the middle-aged women, whose survival rate is very low due to late symptomatic diagnosis. DNA methylation has become one of the key molecular mechanisms in the tumorigenesis of gallbladder. Various molecules have been reported to be epigenetically altered in GBC. In this review, we have discussed the classes of epigenetics, an overview of DNA methylation, technological approaches for its study, profile of methylated genes, their likely roles in GBC, future prospects of biomarker development and other discovery approaches, including therapeutics. © 2016 John Wiley & Sons Australia, Ltd.

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

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

Sluggish gallbladder emptying and gastrointestinal transit after intake of common alcoholic beverages.

PubMed

Kasicka-Jonderko, A; Jonderko, K; Gajek, E; Piekielniak, A; Zawislan, R

2014-02-01

To study the movement along the gut and the effect upon the gallbladder volume of alcoholic beverages taken in the interdigestive state. The study comprised three research blocks attended by 12 healthy subjects each. Within a given research block volunteers underwent three examination sessions held on separate days, being offered an alcoholic beverage, or an aqueous ethanol solution of an identical proof, or a corresponding volume of isotonic glucose solution; the order of administration of the drinks was randomized. The beverages tested were: beer (4.7% vol, 400 ml), red wine (13.7% vol, 200 ml), whisky (43.5% vol, 100 ml) within the "Beer", "Wine", and "Whisky" research block, respectively. Gastric myoelectrical activity was examined electrogastrographically, gastric emptying with ¹³C-sodium acetate breath test, orocaecal transit with lactulose H₂ breath test, gallbladder emptying with ultrasonography, breath ethanol with alcotest. The study showed that alcoholic beverages were emptied from the stomach significantly slower than isotonic glucose. Alcoholic beverages produced by fermentation only (beer, red wine) were emptied from the stomach more slowly than ethanol solutions of identical proof, while gastric evacuation of whisky (distillation product) and matching alcohol solution was similar. The slower gastric evacuation of alcoholic beverages and ethanol solutions could not be ascribed to a disorganization of the gastric myoelectrical activity. The orocaecal transit of beer and red wine did not differ from that of isotonic glucose, whereas the orocaecal transit of whisky and high proof ethanol was markedly prolonged. Red wine and whisky, and to a similar extent control ethanol solutions caused an inhibition and delay of gallbladder emptying. We concluded that alcoholic beverages taken on an empty stomach exert a suppressive effect upon the transport function of the digestive tract and gallbladder emptying. The extent of this action depends on the type of a

Biofilm Producing Salmonella Typhi: Chronic Colonization and Development of Gallbladder Cancer

PubMed Central

Cavallo, Ilaria; Pontone, Martina; Toma, Luigi; Ensoli, Fabrizio

2017-01-01

Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S. Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S. Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S. Typhi strains would be key for effective therapeutic management and cancer prevention. PMID:28858232

A population-based case-control study of cancer of the bile ducts and gallbladder in Quebec, Canada.

PubMed

Ghadirian, P; Simard, A; Baillargeon, J

1993-01-01

In a population-based case-control study of pancreatic cancer in Greater Montreal between 1984 and 1988, a total of 24 patients with cancer of the bile ducts and 33 patients suffering from cancer of the gallbladder were compared to 239 population-based controls. This study was part of the SEARCH program of the International Agency for Research on Cancer. In cases of cancer of the bile ducts, smoking nonfiltered cigarettes produced a relative risk of 2.82 and a 95% confidence interval of 1.01-7.86 after adjustment for age, sex, other smoking habits, alcohol consumption, schooling, and respondent status. Laxative intake was associated with a risk of 2.87 (1.00-8.22). Coffee drinkers were collectively at lower risk than non-drinkers: OR = 0.26 (0.07-0.95). In patients with cancer of the gallbladder, constipation was related to a risk of 3.19 (1.02-9.95) after adjustment for the same factors. In cases with previous gallbladder problems, the risk was found to be significant [OR = 7.96 (2.03-31.2)], 8 times greater in cases than in controls.

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.

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

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.

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

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.

MUC Expression in Gallbladder Epithelial Tissues in Cholesterol-Associated Gallbladder Disease

PubMed Central

Yoo, Kyo-Sang; Choi, Ho Soon; Jun, Dae Won; Lee, Hang Lak; Lee, Oh Young; Yoon, Byung Chul; Lee, Kyeong Geun; Paik, Seung Sam; Kim, Yong Seok; Lee, Jin

2016-01-01

Background/Aims Gallstone pathogenesis is linked to mucin hypersecretion and bacterial infection. Several mucin genes have been identified in gallbladder epithelial cells (GBECs). We investigated MUC expression in cholesterol-associated gallbladder disease and evaluated the relationship between mucin and bacterial infection. Methods The present study involved 20 patients with cholesterol stones with cholecystitis, five with cholesterol stones with cholesterolosis, six with cholesterol polyps, two with gallbladder cancer, and six controls. Canine GBECs treated with lipopolysaccharide were also studied. MUC3, MUC5AC, MUC5B, and MUC6 antibodies were used for dot/slot immunoblotting and immunohistochemical studies of the gallbladder epithelial tissues, canine GBECs, and bile. Reverse-transcription polymerase chain reaction was performed to evaluate MUC3 and MUC5B expression. Results MUC3, MUC5AC, MUC5B, and MUC6 were expressed in the normal gallbladder epithelium, and of those, MUC3 and MUC5B exhibited the highest expression levels. Greatly increased levels of MUC3 and MUC5B expression were observed in the cholesterol stone group, and slightly increased levels were observed in the cholesterol polyp group; MUC3 and MUC5B mRNA was also upregulated in those groups. Canine GBECs treated with lipopolysaccharide also showed upregulation of MUC3 and MUC5B. Conclusions The mucin genes with the highest expression levels in gallbladder tissue in cholesterol-associated diseases were MUC3 and MUC5B. Cholesterol stones and gallbladder infections were associated with increased MUC3 and MUC5B expression. PMID:27563024

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.

Safety and Immune Response to a Multi-component Immune Based Therapy (MKC1106-PP) for Patients With Advanced Cancer.

ClinicalTrials.gov

2010-08-02

Ovarian; Melanoma; Renal; Prostate; Colorectal; Endometrial Carcinoma; Cervical Carcinoma; Testicular Cancer; Thyroid Cancer; Small Cell Lung Carcinoma; Mesothelioma; Breast Carcinoma; Esophageal Carcinoma; Gastric Cancer; Pancreatic Carcinoma; Neuroendocrine Cancer; Liver Cancer; Gallbladder Cancer; Biliary Tract Cancer; Anal Carcinoma; Bone Sarcomas; Soft Tissue Sarcomas; Carcinoma of Unknown Origin, Primary

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

Inhibitory effect of Survivin promoter-regulated oncolytic adenovirus carrying P53 gene against gallbladder cancer.

PubMed

Liu, Chen; Sun, Bin; An, Ni; Tan, Weifeng; Cao, Lu; Luo, Xiangji; Yu, Yong; Feng, Feiling; Li, Bin; Wu, Mengchao; Su, Changqing; Jiang, Xiaoqing

2011-12-01

Gene therapy has become an important strategy for treatment of malignancies, but problems remains concerning the low gene transferring efficiency, poor transgene expression and limited targeting specific tumors, which have greatly hampered the clinical application of tumor gene therapy. Gallbladder cancer is characterized by rapid progress, poor prognosis, and aberrantly high expression of Survivin. In the present study, we used a human tumor-specific Survivin promoter-regulated oncolytic adenovirus vector carrying P53 gene, whose anti-cancer effect has been widely confirmed, to construct a wide spectrum, specific, safe, effective gene-viral therapy system, AdSurp-P53. Examining expression of enhanced green fluorecent protein (EGFP), E1A and the target gene P53 in the oncolytic adenovirus system validated that Survivin promoter-regulated oncolytic adenovirus had high proliferation activity and high P53 expression in Survivin-positive gallbladder cancer cells. Our in vitro cytotoxicity experiment demonstrated that AdSurp-P53 possessed a stronger cytotoxic effect against gallbladder cancer cells and hepatic cancer cells. The survival rate of EH-GB1 cells was lower than 40% after infection of AdSurp-P53 at multiplicity of infection (MOI) = 1 pfu/cell, while the rate was higher than 90% after infection of Ad-P53 at the same MOI, demonstrating that AdSurp-P53 has a potent cytotoxicity against EH-GB1 cells. The tumor growth was greatly inhibited in nude mice bearing EH-GB1 xenografts when the total dose of AdSurp-P53 was 1 × 10(9) pfu, and terminal dUTP nick end-labeling (TUNEL) revealed that the apoptotic rate of cancer cells was (33.4 ± 8.4)%. This oncolytic adenovirus system overcomes the long-standing shortcomings of gene therapy: poor transgene expression and targeting of only specific tumors, with its therapeutic effect better than the traditional Ad-P53 therapy regimen already on market; our system might be used for patients with advanced gallbladder cancer and

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.

Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile

PubMed Central

González Silos, Rosa; Marcelain, Katherine; Baez Benavides, Pablo; Barahona Ponce, Carol; Fischer, Christine; Peil, Barbara; Sinsheimer, Janet; Barajas, Olga; Gonzalez-Jose, Rolando; Cátira Bortolini, Maria; Canizales-Quinteros, Samuel; Gallo, Carla; Ruiz Linares, Andres; Rothhammer, Francisco

2017-01-01

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1–4.3%, P = 6×10−27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data. PMID:28542165

Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile.

PubMed

Lorenzo Bermejo, Justo; Boekstegers, Felix; González Silos, Rosa; Marcelain, Katherine; Baez Benavides, Pablo; Barahona Ponce, Carol; Müller, Bettina; Ferreccio, Catterina; Koshiol, Jill; Fischer, Christine; Peil, Barbara; Sinsheimer, Janet; Fuentes Guajardo, Macarena; Barajas, Olga; Gonzalez-Jose, Rolando; Bedoya, Gabriel; Cátira Bortolini, Maria; Canizales-Quinteros, Samuel; Gallo, Carla; Ruiz Linares, Andres; Rothhammer, Francisco

2017-05-01

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1-4.3%, P = 6×10-27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.

Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder

ClinicalTrials.gov

2017-06-13

Adenocarcinoma of the Extrahepatic Bile Duct; Adenocarcinoma of the Gallbladder; Advanced Adult Primary Liver Cancer; Gastrointestinal Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder 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.

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.

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.

Systematic alphanumeric-coded endoscopy versus chromoendoscopy for the detection of precancerous gastric lesions and early gastric cancer in subjects at average risk for gastric cancer.

PubMed

Pérez-Mendoza, A; Zárate-Guzmán, Á M; Galvis García, E S; Sobrino Cossío, S; Djamus Birch, J

Gastric cancer is one of the main causes of cancer worldwide, but there is currently no global screening strategy for the disease. Endoscopy is the screening method of choice in some Asian countries, but no standardized technique has been recognized. Systematic alphanumeric-coded endoscopy can increase gastric lesion detection. The aim of the present article was to compare the usefulness of systematic alphanumeric-coded endoscopy with conventional endoscopy for the detection of premalignant lesions and early gastric cancer in subjects at average risk for gastric cancer. A cross-sectional, comparative, prospective, randomized study was conducted on patients at average risk for gastric cancer (40-50 years of age, no history of H. pylori infection, intestinal metaplasia, gastric atrophy, or gastrointestinal surgery). Before undergoing endoscopy, the patients had gastric preparation (200mg of oral acetylcysteine or 50mg of oral dimethicone). Conventional chromoendoscopy was performed with indigo carmine dye for contrast enhancement. Fifty consecutive cases (mean age 44.4 ± 3.34 years, 60% women, BMI 27.6 ± 5.82 kg/m 2 ) were evaluated. Endoscopic imaging quality was satisfactory in all the cases, with no differences between methods (p = 0.817). The detection rate of premalignant lesions and early gastric cancer was 14% (6 cases of intestinal metaplasia and one case of gastric adenocarcinoma). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 100, 95, 80, 100 and 96%, respectively, for systematic alphanumeric-coded endoscopy, and 100, 45, 20, 100, and 52%, respectively, for conventional endoscopy. Lesion detection through systematic alphanumeric-coded endoscopy was superior to that of conventional endoscopy (p = 0.003; OR = 12). Both techniques were effective, but systematic alphanumeric-coded endoscopy significantly reduced the false positive rate. Copyright © 2018 Asociación Mexicana de

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.

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.

Lobular breast cancer metastasis to the colon, the appendix and the gallbladder.

PubMed

Molina-Barea, Rocio; Rios-Peregrina, Rosa M; Slim, Mahmoud; Calandre, Elena P; Hernández-García, Maria D; Jimenez-Rios, José A

2014-12-01

Metastases of lobular breast cancer are commonly encountered at the level of lungs, bones, brain and liver, whereas lesions in the gastrointestinal tract are rarely seen. A case of a patient with metastases in the right colon and gallbladder originating from an invasive lobular carcinoma is described. Adequate diagnostic procedures should be performed in patients with a history of breast cancer and who show gastrointestinal symptoms to rule out the potential presence of gastrointestinal metastases.

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

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

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

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.

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.

[Quality of DNA from archival pathological samples of gallbladder cancer].

PubMed

Roa, Iván; de Toro, Gonzalo; Sánchez, Tamara; Slater, Jeannie; Ziegler, Anne Marie; Game, Anakaren; Arellano, Leonardo; Schalper, Kurt; de Aretxabala, Xabier

2013-12-01

The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies. To determine the quality of DNA extracted from gallbladder cancer samples at different institutions. One hundred ninety four samples coming from five medical centers in Chile, were analyzed. DNA extraction was quantified determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (β-globin products of 110, 268 and 501 base pairs). The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics. Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.

[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.

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.

[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.

Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer.

PubMed

Alvarez, Hector; Corvalan, Alejandro; Roa, Juan C; Argani, Pedram; Murillo, Francisco; Edwards, Jennifer; Beaty, Robert; Feldmann, Georg; Hong, Seung-Mo; Mullendore, Michael; Roa, Ivan; Ibañez, Luis; Pimentel, Fernando; Diaz, Alfonso; Riggins, Gregory J; Maitra, Anirban

2008-05-01

Gallbladder cancer (GBC) is an uncommon neoplasm in the United States, but one with high mortality rates. This malignancy remains largely understudied at the molecular level such that few targeted therapies or predictive biomarkers exist. We built the first series of serial analysis of gene expression (SAGE) libraries from GBC and nonneoplastic gallbladder mucosa, composed of 21-bp long-SAGE tags. SAGE libraries were generated from three stage-matched GBC patients (representing Hispanic/Latino, Native American, and Caucasian ethnicities, respectively) and one histologically alithiasic gallbladder. Real-time quantitative PCR was done on microdissected epithelium from five matched GBC and corresponding nonneoplastic gallbladder mucosa. Immunohistochemical analysis was done on a panel of 182 archival GBC in high-throughput tissue microarray format. SAGE tags corresponding to connective tissue growth factor (CTGF) transcripts were identified as differentially overexpressed in all pairwise comparisons of GBC (P < 0.001). Real-time quantitative PCR confirmed significant overexpression of CTGF transcripts in microdissected primary GBC (P < 0.05), but not in metastatic GBC, compared with nonneoplastic gallbladder epithelium. By immunohistochemistry, 66 of 182 (36%) GBC had high CTGF antigen labeling, which was significantly associated with better survival on univariate analysis (P = 0.0069, log-rank test). An unbiased analysis of the GBC transcriptome by SAGE has identified CTGF expression as a predictive biomarker of favorable prognosis in this malignancy. The SAGE libraries from GBC and nonneoplastic gallbladder mucosa are publicly available at the Cancer Genome Anatomy Project web site and should facilitate much needed research into this lethal neoplasm.

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

Routine histological analysis of a macroscopically normal gallbladder--a review of the literature.

PubMed

Jamal, K; Ratansingham, K; Siddique, M; Nehra, D

2014-01-01

70,000 cholecystectomies were performed in the United Kingdom in 2011-2012. Currently it is standard practice to submit all gallbladder specimens for routine histology to exclude malignancy. The aim of this systematic review was to establish whether a normal macroscopic appearance to the gallbladder at the time of cholecystectomy is sufficient to rule out malignancy and therefore negate the need for routine histology. Relevant articles that were published between 1966 and January 2013 were identified through electronic databases. 21 studies reported on 34,499 histologically analysed specimens. 172/187 (92%) of gallbladder cancers demonstrated intra-operative macroscopic abnormality. Studies that opened the specimens intra-operatively identified all cancers, whereas gross macroscopic visualization resulted in 15 potentially missed cancers (p = 0.10). In patients of European ethnicity, gallbladder cancer in a macroscopically normal looking gallbladder was identified in only one study; however all of these patients were above the age of 60. The incidence of gallbladder cancer was significantly raised in ethnic groups from high risk areas (p = 0.0001). A macroscopically normal gallbladder in patients of European ethnicity under the age of 60 may not require formal histopathology. The best method for intra-operative examination may involve opening the specimen to allow inspection of the mucosa and wall, however this needs further investigation. In the context of the volume of gallbladder surgery being performed there is the potential for significant cost and time savings. Copyright © 2014 Surgical Associates Ltd. All rights reserved.

Epidemiology of gastric cancer in Japan

PubMed Central

Inoue, M; Tsugane, S

2005-01-01

Despite its decreasing trend in Japan, gastric cancer remains an important public health problem. Although the age standardised rates of gastric cancer have been declining for decades, the absolute numbers are increasing because of the rapid aging of the population. A large proportion of Japanese gastric cancers are detected at an early stage, with a better overall survival rate. As with Western developed countries, a change in the social environment such as reduced salt use and increased fresh vegetable and fruit intake as well as improvement of food storage may play an important part in the decline. Differences in Helicobacter pylori infection rates between generations presumably have contributed to the generation related variation in the declining trends. It is expected that most gastric cancers in Japan may be preventable by lifestyle modification such as salt reduction and increased fruit and vegetable intake, together with avoidance of smoking and countermeasures against H pylori infection so that the level now evident in Western developed countries can be reached. PMID:15998815

[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.

Gallic acid loaded PEO-core/zein-shell nanofibers for chemopreventive action on gallbladder cancer cells.

PubMed

Acevedo, Francisca; Hermosilla, Jeyson; Sanhueza, Claudia; Mora-Lagos, Barbara; Fuentes, Irma; Rubilar, Mónica; Concheiro, Angel; Alvarez-Lorenzo, Carmen

2018-07-01

Coaxial electrospinning was used to develop gallic acid (GA) loaded poly(ethylene oxide)/zein nanofibers in order to improve its chemopreventive action on human gallbladder cancer cells. Using a Plackett-Burman design, the effects of poly(ethylene oxide) and zein concentration and applied voltage on the diameter and morphology index of nanofibers were investigated. Coaxial nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). GA loading efficiency as high as 77% was obtained under optimal process conditions. The coaxial nanofibers controlled GA release in acid and neutral pH medium. Cytotoxicity and reactive oxygen species (ROS) production on gallbladder cancer cell lines GB-d1 and NOZ in the presence of GA-nanofibers were assessed. GA-nanofibers triggered an increase in the cellular cytotoxicity compared with free GA on GB-d1 and NOZ cells. Statistically significant differences were found in ROS levels of GA-nanofibers compared with free GA on NOZ cells. Differently, ROS production on GB-d1 cell line was similar. Based on these results, the coaxial nanofibers obtained in this study under optimized operational conditions offer an alternative for the development of a GA release system with improved chemopreventive action on gallbladder cancer cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Sequential occurrence of preneoplastic lesions and accumulation of loss of heterozygosity in patients with gallbladder stones suggest causal association with gallbladder cancer.

PubMed

Jain, Kajal; Mohapatra, Trilochan; Das, Prasenjit; Misra, Mahesh Chandra; Gupta, Siddhartha Datta; Ghosh, Manju; Kabra, Madhulika; Bansal, Virinder Kumar; Kumar, Subodh; Sreenivas, Vishnubhatla; Garg, Pramod Kumar

2014-12-01

Causal association of gallbladder stones with gallbladder cancer (GBC) is not yet well established. To study the frequency of occurrence of preneoplastic histological lesions and loss of heterozygosity (LOH) of tumor suppressor genes in patients with gallstones. All consecutive patients with gallstones undergoing cholecystectomy from 2007-2011 were included prospectively. Histological examination of the gallbladder specimens was done for preneoplastic lesions. LOH at 8 loci, that is 3p12, 3p14.2, 5q21, 9p21, 9q, 13q, 17p13, and 18q for tumor suppressor genes (DUTT1, FHIT, APC, p16, FCMD, RB1, p53, and DCC genes) that are associated with GBC was tested from microdissected preneoplastic lesions using microsatellite markers. These LOH were also tested in 30 GBC specimens. Of the 350 gallbladder specimens from gallstone patients, hyperplasia was found in 32%, metaplasia in 47.8%, dysplasia in 15.7%, and carcinoma in situ in 0.6%. Hyperplasia, metaplasia, and dysplasia alone were found in 11.7%, 24.6%, and 1.4% of patients, respectively. A combination of hyperplasia and dysplasia, metaplasia and dysplasia, and hyperplasia, metaplasia, and dysplasia was found in 3.4%, 6.3%, and 4.3% of patients, respectively. LOH was present in 2.1% to 47.8% of all the preneoplastic lesions at different loci. Fractional allelic loss was significantly higher in those with dysplasia compared with other preneoplastic lesions (0.31 vs 0.22; P = 0.042). No preneoplastic lesion or LOH was found in normal gallbladders. Patients with gallstones had a high frequency of preneoplastic lesions and accumulation of LOH at various tumor suppressor genes, suggesting a possible causal association of gallstones with GBC.

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

Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection

PubMed Central

Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

2015-01-01

AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. METHODS: A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. RESULTS: Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal

Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection.

PubMed

Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

2015-07-21

To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal metaplasia score of

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.

Connective tissue growth factor immunohistochemical expression is associated with gallbladder cancer progression.

PubMed

Garcia, Patricia; Leal, Pamela; Alvarez, Hector; Brebi, Priscilla; Ili, Carmen; Tapia, Oscar; Roa, Juan C

2013-02-01

Gallbladder cancer (GBC) is an aggressive neoplasia associated with late diagnosis, unsatisfactory treatment, and poor prognosis. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. Connective tissue growth factor (CTGF) is thought to play a role in the pathologic processes and is overexpressed in several human cancers, including GBC. No information is available about CTGF expression in early stages of gallbladder carcinogenesis. Objective.- To evaluate the expression level of CTGF in benign and malignant lesions of gallbladder and its correlation with clinicopathologic features and GBC prognosis. Connective tissue growth factor protein was examined by immunohistochemistry on tissue microarrays containing tissue samples of chronic cholecystitis (n = 51), dysplasia (n = 15), and GBC (n = 169). The samples were scored according to intensity of staining as low/absent and high CTGF expressers. Statistical analysis was performed using the χ(2) test or Fisher exact probability test with a significance level of P < .05. Survival analysis was assessed by the Kaplan-Meier method and the log-rank test. Connective tissue growth factor expression showed a progressive increase from chronic cholecystitis to dysplasia and then to early and advanced carcinoma. Immunohistochemical expression (score ≥2) was significantly higher in advanced tumors, in comparison with chronic cholecystitis (P < .001) and dysplasia (P = .03). High levels of CTGF expression correlated with better survival (P = .04). Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.

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

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

Spontaneous cholecystocutaneous fistula as a primary manifestation of gallbladder adenocarcinoma associated with gallbladder lithiasis - case report.

PubMed

Micu, Bogdan Vasile; Andercou, Octavian Aurel; Micu, Carmen Maria; Militaru, Valentin; Jeican, IonuŢ Isaia; Bungărdean, Cătălina Ileana; Mogoantă, Stelian ŞtefăniŢă; Miclăuş, Dan Radu; Pop, Tudor Radu

2017-01-01

Spontaneous cholecystocutaneous fistula (SCF) is a rare complication of neglected calculous biliary disease and also an extremely rare complication of gallbladder neoplasm. This pathology has become even rarer because of prompt diagnosis and expedient surgical intervention for gallstones. So far, there is one published report of a SCF due to gallbladder adenocarcinoma. We present the case of a woman aged 87 years, admitted to the Vth Department of Surgery, Clinical Municipal Hospital of Cluj-Napoca (Romania) for a tumoral mass located in the epigastrium. In the epigastrium, the patient had three skin orifices of about 1-2 mm each, through which purulent secretion occurred. The abdominal ultrasound highlighted a cholecystocutaneous fistula with the presence of a subcutaneous gallstone. Intraoperatively, we found a cholecystocutaneous fistula, a 1 cm subcutaneous gallstone, gallbladder with thickened walls containing a cylinder-shaped gallstone of 5÷3 cm. Fistulectomy, gallstones extraction and cholecystectomy were performed. The histopathological examination highlighted gallbladder adenocarcinoma. In conclusion, SCF can be the first significant manifestation of gallbladder cancer associated with neglected calculous biliary disease.

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.

Inhibition of connective tissue growth factor (CTGF/CCN2) in gallbladder cancer cells leads to decreased growth in vitro

PubMed Central

Garcia, Patricia; Leal, Pamela; Ili, Carmen; Brebi, Priscilla; Alvarez, Hector; Roa, Juan C

2013-01-01

Gallbladder cancer (GBC) is an aggressive neoplasm associated with late diagnosis, unsatisfactory treatment and poor prognosis. Previous work showed that connective tissue growth factor (CTGF) expression is increased in this malignancy. This matricellular protein plays an important role in various cellular processes and its involvement in the tumorigenesis of several human cancers has been demonstrated. However, the precise function of CTGF expression in cancer cells is yet to be determined. The aim of this study was to evaluate the CTGF expression in gallbladder cancer cell lines, and its effect on cell viability, colony formation and in vitro cell migration. CTGF expression was evaluated in seven GBC cell lines by Western blot assay. Endogenous CTGF expression was downregulated by lentiviral shRNA directed against CTGF mRNA in G-415 cells, and the effects on cell viability, anchorage-independent growth and migration was assessed by comparing them to scrambled vector-transfected cells. Knockdown of CTGF resulted in significant reduction in cell viability, colony formation and anchorage-independent growth (P < 0.05). An increased p27 expression was observed in G-415 cells with loss of CTGF function. Our results suggest that high expression of this protein in gallbladder cancer may confer a growth advantage for neoplastic cells. PMID:23593935

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

[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

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.

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.

Value of contrast-enhanced ultrasound in the differential diagnosis of gallbladder lesion

PubMed Central

Zhang, Hui-Ping; Bai, Min; Gu, Ji-Ying; He, Ying-Qian; Qiao, Xiao-Hui; Du, Lian-Fang

2018-01-01

AIM To describe contrast-enhanced ultrasound (CEUS) features and evaluate differential diagnosis value of CEUS and conventional ultrasound for patients with benign and malignant gallbladder lesions. METHODS This study included 105 gallbladder lesions. Before surgical resection and pathological examination, conventional ultrasound and CEUS were performed to examine for lesions. Then, all the lesions were diagnosed as (1) benign, (2) probably benign, (3) probably malignant or (4) malignant using both conventional ultrasound and CEUS. The CEUS features of these gallbladder lesions were analyzed and diagnostic efficiency between conventional ultrasound and CEUS was compared. RESULTS There were total 17 cases of gallbladder cancer and 88 cases of benign lesion. Some gallbladder lesions had typical characteristics on CEUS (e.g., gallbladder adenomyomatosis had typical characteristics of small nonenhanced areas on CEUS). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CEUS were 94.1%, 95.5%, 80.0%, 98.8% and 95.2%, respectively. These were significantly higher than conventional ultrasound (82.4%, 89.8%, 60.9%, 96.3% and 88.6%, respectively). CEUS had an accuracy of 100% for gallbladder sludge and CEUS helped in differential diagnosis among gallbladder polyps, gallbladder adenoma and gallbladder cancer. CONCLUSION CEUS may provide more useful information and improve the diagnosis efficiency for the diagnosis of gallbladder lesions than conventional ultrasound. PMID:29456413

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.

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

Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study

PubMed Central

Shindoh, Junichi; de Aretxabala, Xabier; Aloia, Thomas A.; Carlos Roa, Juan; Zimmitti, Giuseppe; Javle, Milind; Conrad, Claudius; Maru, Dipen M.; Aoki, Taku; Vigano, Luca; Ribero, Dario; Roa, Ivan; Kokudo, Norihiro; Capussotti, Lorenzo; Vauthey, Jean-Nicolas

2016-01-01

Objective To determine the prognostic impact of tumor location in gallbladder cancer. Summary Background Data Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear. Methods For 437 patients with gallbladder cancer resected at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as “hepatic side” or “peritoneal side”, and the prognostic significance of tumor location was evaluated. Results Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n=99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n=153) (51% vs. 19%, 33% vs. 8%, and 40% vs. 17%, respectively, P<0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P=0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% CI, 1.7 to 4.2; P<0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs. 3%, P=0.003) and distant lymph nodes (16% vs. 3%, P=0.019) even after radical resection. Conclusions After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival. PMID:24854451

Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study.

PubMed

Shindoh, Junichi; de Aretxabala, Xabier; Aloia, Thomas A; Roa, Juan Carlos; Roa, Ivan; Zimmitti, Giuseppe; Javle, Milind; Conrad, Claudius; Maru, Dipen M; Aoki, Taku; Vigano, Luca; Ribero, Dario; Kokudo, Norihiro; Capussotti, Lorenzo; Vauthey, Jean-Nicolas

2015-04-01

To determine the prognostic impact of tumor location in gallbladder cancer. Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear. For 437 patients with gallbladder cancer who underwent resection at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as "hepatic side" or "peritoneal side," and the prognostic significance of tumor location was evaluated. Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n = 99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n = 153) (51% vs 19%, 33% vs 8%, and 40% vs 17%, respectively; P < 0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P = 0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% confidence interval, 1.7-4.2; P < 0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs 3%; P = 0.003) and distant lymph nodes (16% vs 3%; P = 0.019) even after radical resection. After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival.

Estrogen-dependent gallbladder carcinogenesis in LXRbeta-/- female mice.

PubMed

Gabbi, Chiara; Kim, Hyun-Jin; Barros, Rodrigo; Korach-Andrè, Marion; Warner, Margaret; Gustafsson, Jan-Ake

2010-08-17

Gallbladder cancer is a highly aggressive disease with poor prognosis that is two to six times more frequent in women than men. The development of gallbladder cancer occurs over a long time (more than 15 y) and evolves from chronic inflammation to dysplasia/metaplasia, carcinoma in situ, and invasive carcinoma. In the present study we found that, in female mice in which the oxysterol receptor liver X receptor-beta (LXRbeta) has been inactivated, preneoplastic lesions of the gallbladder developed and evolved to cancer in old animals. LXRbeta is a nuclear receptor involved in the control of lipid homeostasis, glucose metabolism, inflammation, proliferation, and CNS development. LXRbeta(-/-) female gallbladders were severely inflamed, with regions of dysplasia and high cell density, hyperchromasia, metaplasia, and adenomas. No abnormalities were evident in male mice, nor in LXRalpha(-/-) or LXRalpha(-/-)beta(-/-) animals of either sex. Interestingly, the elimination of estrogens with ovariectomy prevented development of preneoplastic lesions in LXRbeta(-/-) mice. The etiopathological mechanism seems to involve TGF-beta signaling, as the precancerous lesions were characterized by strong nuclear reactivity of phospho-SMAD-2 and SMAD-4 and loss of E-cadherin expression. Upon ovariectomy, E-cadherin was reexpressed on the cell membranes and immunoreactivity of pSMAD-2 in the nuclei was reduced. These findings suggest that LXRbeta in a complex interplay with estrogens and TGF-beta could play a crucial role in the malignant transformation of the gallbladder epithelium.

Polyp on ultrasound: now what? The association between gallbladder polyps and cancer.

PubMed

Donald, Graham; Sunjaya, Dharma; Donahue, Timothy; Hines, O Joe

2013-10-01

The association between gallbladder polyps (GBP) and gallbladder cancer (GBC) is unclear. We sought to determine the association between preoperative diagnosis of GBP on imaging and GBC. A retrospective review of patients over 9 years was conducted using International Classification of Diseases, 9th Revision codes for GBP and GBC who underwent cholecystectomy at our institution. Demographics, imaging findings, and pathology results were recorded. A total of 2416 patients underwent cholecystectomy during the study period. Twenty-seven had an operation for GBP either as a result of concern for size or symptoms. Polyp sizes were categorized as less than 1 cm, 1 to 2 cm, or 2 cm or greater. Twenty-four patients in this group (88.9%) had no evidence of high-grade dysplasia or cancer and all of these benign polyps were 2 cm or less on imaging. One patient with a 2.4-cm polyp had high-grade dysplasia, and two patients with polyps over 3 cm had adenocarcinoma. During the same period, 20 patients had an operation for GBC with two patients common to the polyp group. The group of patients with noncancerous polyps was significantly younger than the cancer group (polyps and no polyps). The cancer group was more likely to be symptomatic. Therefore, polyps over 2 cm should be removed given the risk of high-grade dysplasia and cancer above this size. Polyps less than 2 cm were not associated with high-grade dysplasia or cancer and thus surgery may not be required. Intermediate- and small-sized polyps can be monitored with serial ultrasound, especially in younger, asymptomatic patients in whom the risk of malignancy is low.

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

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

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.

Emodin As an Effective Agent in Targeting Cancer Stem-Like Side Population Cells of Gallbladder Carcinoma

PubMed Central

Li, Xin-xing; Dong, Ying; Wang, Wei; Wang, Hao-lu; Chen, Yu-ying; Shi, Gui-ying; Yi, Jing

2013-01-01

Side population (SP) cells are previously identified from bone marrow based on their capacity to efflux of the fluorescent dye Hoechst 33342. Recent studies demonstrate that SP cells isolated from various cancer cell lines and primary tumors possess stem-cell-like properties. Thus, targeting tumor SP cells may provide new strategies for treatment in clinic. We previously showed that 1,3,8-trihydroxy-6-methylanthraquinone (emodin), a reactive oxygen species (ROS) generator, enhanced sensitivity of gallbladder cancer SGC-996 cells to cisplatin (CDDP) via generation of ROS and downregulation of multidrug-resistance-associated protein 1 (MRP1). To determine whether emodin also acts effectively on cancer stem cells of gallbladder carcinoma, we use SP cells as a model of cancer stem-cell-like cells. Here, we found that emodin, via ROS-related mechanism and suppressing the function of ATP-binding cassette super-family G member (ABCG2), which is known to be associated with Hoechst dye efflux activity of SP cells, not only reduced the ratio, inhibited clone formation, and eliminated sphere formation of SP cells effectively, but also promoted obviously the intracellular accumulation of doxorubicin, the main substrate of the efflux pump ABCG2. In addition, emodin could sensitize CDDP, via inhibition of expression of ABCG2, to overcome chemoresistance of SP cells. Importantly, similar to the experiment in vitro, emodin/CDDP co-treatment in vivo suppressed the tumor growth derived from SP cells through downregulating ABCG2 expression. Our results suggest that emodin is an effective agent targeting cancer stem-like SP cells of gallbladder carcinoma, either alone or acts as a chemotherapy enhancer. PMID:22974371

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

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.

Inhibition of connective tissue growth factor (CTGF/CCN2) in gallbladder cancer cells leads to decreased growth in vitro.

PubMed

Garcia, Patricia; Leal, Pamela; Ili, Carmen; Brebi, Priscilla; Alvarez, Hector; Roa, Juan C

2013-06-01

Gallbladder cancer (GBC) is an aggressive neoplasm associated with late diagnosis, unsatisfactory treatment and poor prognosis. Previous work showed that connective tissue growth factor (CTGF) expression is increased in this malignancy. This matricellular protein plays an important role in various cellular processes and its involvement in the tumorigenesis of several human cancers has been demonstrated. However, the precise function of CTGF expression in cancer cells is yet to be determined. The aim of this study was to evaluate the CTGF expression in gallbladder cancer cell lines, and its effect on cell viability, colony formation and in vitro cell migration. CTGF expression was evaluated in seven GBC cell lines by Western blot assay. Endogenous CTGF expression was downregulated by lentiviral shRNA directed against CTGF mRNA in G-415 cells, and the effects on cell viability, anchorage-independent growth and migration was assessed by comparing them to scrambled vector-transfected cells. Knockdown of CTGF resulted in significant reduction in cell viability, colony formation and anchorage-independent growth (P < 0.05). An increased p27 expression was observed in G-415 cells with loss of CTGF function. Our results suggest that high expression of this protein in gallbladder cancer may confer a growth advantage for neoplastic cells. © 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

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.

Gallbladder carcinoma: Prognostic factors and therapeutic options

PubMed Central

Goetze, Thorsten Oliver

2015-01-01

The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ‘‘incidental or occult gallbladder carcinoma’’ (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2

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.

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.

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

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.

High rates of advanced gastric cancer in community of Flushing, New York.

PubMed

Dinani, Amreen; Desai, Amit; Kohn, Nina; Gutkin, Ellen; Nussbaum, Michel; Somnay, Kaumudi

2012-03-01

Gastric cancer remains a major public health issue and is a leading cause of death worldwide, accounting for 600,000 deaths annually. Over the last decades, there has been a steady decline in the incidence rates of gastric cancer. Furthermore, the incidence rates of gastric cancer in different parts of the country vary due to epidemiological and migration trends. Despite these trends, several studies that have continued to observe high rates of gastric cancer in populations that come from high-risk regions. The aim of the study was to describe the gastric cancer patients presenting NYHQ with an emphasis on those presenting at a young age and advanced disease. A subanalysis of the Asian population was also done, which is considered a high-risk group. Consecutive chart review of patients admitted with gastric cancer from January 2000 to August 2008 was extracted from the Oncology registry at NYHQ. Parameters that were evaluated were age, sex, race, type of gastric cancer, and stage of gastric cancer at initial presentation. The SAS/PC software package (SAS Institute Inc., Cary, NC) was employed for statistical analyses. Four hundred fifty-seven patients were diagnosed with gastric cancer. Approximately one third of the total patients were younger than 60 years of age. Of the Asian patients, almost half the patients (48.8%) had advanced disease of which two thirds were under the age of 60 years. The rates of advanced gastric cancer observed at NYHQ are significant and comparable to recent epidemiology literature on rates in Asian populations in Asia. Communities, like Flushing, NY, may benefit from early detection of gastric cancers, similar to those instituted in Japan and Taiwan.

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.

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.

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

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

Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma.

PubMed

Yuan, Hai-Xia; Cao, Jia-Ying; Kong, Wen-Tao; Xia, Han-Sheng; Wang, Xi; Wang, Wen-Ping

2015-04-01

Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection. It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations. The study aimed to illustrate characteristics of contrast-enhanced ultrasound (CEUS) and its diagnostic value in gallbladder adenoma. Thirty-seven patients with 39 gallbladder adenomatoid lesions (maximal diameter ≥10 mm and without metastasis) were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individually among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. Adenoma lesions showed iso-echogenicity in ultrasound, and an eccentric enhancement pattern, "fast-in and synchronous-out" contrast enhancement pattern and homogeneous at peak-time enhancement in CEUS. The homogenicity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion (100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively). The characteristic of the eccentric enhancement pattern had the highest diagnostic ability in differentiating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, respectively. CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps (≥10 mm in diameter). Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.

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

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.

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.

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.

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

Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene: a case report.

PubMed

Mody, Kabir; Strauss, Edward; Lincer, Robert; Frank, Richard C

2010-10-20

Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR) is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI) to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene. A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2) on day 1 and 8 every 21 days as well as daily erlotinib (100 mg). After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found. This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status.

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.

Gallbladder Cancer in the 21st Century

PubMed Central

Kanthan, Rani; Senger, Jenna-Lynn; Ahmed, Shahid; Kanthan, Selliah Chandra

2015-01-01

Gallbladder cancer (GBC) is an uncommon disease in the majority of the world despite being the most common and aggressive malignancy of the biliary tree. Early diagnosis is essential for improved prognosis; however, indolent and nonspecific clinical presentations with a paucity of pathognomonic/predictive radiological features often preclude accurate identification of GBC at an early stage. As such, GBC remains a highly lethal disease, with only 10% of all patients presenting at a stage amenable to surgical resection. Among this select population, continued improvements in survival during the 21st century are attributable to aggressive radical surgery with improved surgical techniques. This paper reviews the current available literature of the 21st century on PubMed and Medline to provide a detailed summary of the epidemiology and risk factors, pathogenesis, clinical presentation, radiology, pathology, management, and prognosis of GBC. PMID:26421012

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

Familial clustering in subgroups of gastric cancer stratified by histology, age group and location.

PubMed

Eto, K; Ohyama, S; Yamaguchi, T; Wada, T; Suzuki, Y; Mitsumori, N; Kashiwagi, H; Anazawa, S; Yanaga, K; Urashima, M

2006-09-01

To assess the risk of gastric cancer in a Japanese patient population with the disease by stratification with histology, age, tumour location and the association with family history of gastric or non-gastric tumours. A retrospective analysis of 1400 consecutive patients with gastric cancer and 13,467 age- and gender-matched controls from a pre-recorded database using conditional logistic regression models. Young patients (< or = 43 years of age) with gastric cancer of intestinal type had a strong association with family history of gastric cancer in first degree-relatives (OR=12.5). Moreover, when a history of gastric cancer was observed in both parents, there was an increased risk of gastric cancer intestinal type (OR=7.8), more commonly in the proximal and mid-stomach. In contrast, there was an increased risk of diffuse-type cancer when both parents suffered non-gastric cancers (OR=2.1). These data suggest that the degree of familial clustering differ in gastric cancer subgroups stratified by histology, age, and stomach location in this Japanese population.

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

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.

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

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.

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.

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.

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

MET amplification as a potential therapeutic target in gastric cancer

PubMed Central

Kawakami, Hisato; Okamoto, Isamu; Arao, Tokuzo; Okamoto, Wataru; Matsumoto, Kazuko; Taniguchi, Hirokazu; Kuwata, Kiyoko; Yamaguchi, Haruka; Nishio, Kazuto; Nakagawa, Kazuhiko; Yamada, Yasuhide

2013-01-01

Our aim was to investigate both the prevalence of MET amplification in gastric cancer as well as the potential of this genetic alteration to serve as a therapeutic target in gastric cancer. MET amplification was assessed by initial screening with a PCR-based copy number assay followed by confirmatory FISH analysis in formalin-fixed, paraffin-embedded specimens of gastric cancer obtained at surgery. The effects of MET tyrosine kinase inhibitors (MET-TKIs) in gastric cancer cells with or without MET amplification were also examined. The median MET copy number in 266 cases of gastric cancer was 1.7, with a range of 0.41 to 21.3. We performed FISH analysis for the 15 cases with the highest MET copy numbers. MET amplification was confirmed in the four assessable cases with a MET copy number of at least 4, whereas MET amplification was not detected in those with a gene copy number of <4. The prevalence of MET amplification was thus 1.5% (4 out of 266 cases). Inhibition of MET by MET-TKIs resulted in the induction of apoptosis accompanied by attenuation of downstream MET signaling in gastric cancer cell lines with MET amplification but not in those without this genetic change. MET amplification identifies a small but clinically important subgroup of gastric cancer patients who are likely to respond to MET-TKIs. Furthermore, screening with a PCR-based copy number assay is an efficient way to reduce the number of patients requiring confirmation of MET amplification by FISH analysis. PMID:23327903

[The present state and future of home care for gastric cancer patients].

PubMed

Maeda, Yoshiharu; Sasaki, Eisaku; Mikoshiba, Michio; Kandabashi, Kouji; Omuro, Yasushi; Okamoto, Rumiko; Sasaki, Tsuneo

2006-05-01

Recently, cancer treatment has been shift from inpatient chemotherapy to outpatient chemotherapy, because of various medical circumstances. In chemotherapy of gastric cancer, outpatient chemotherapy was not spread in the last decade, because the chemotherapy protocol of gastric cancer was not fit for outpatient chemotherapy. But the development of new drugs as TS-1 make outpatient chemotherapy more frequent. So home care of patients has been important for management of gastric cancer. Various symptoms due to obstruction at primary lesion or other lesion prevent patients from living at home in gastric cancer. But recently, technical development and spread of home parenteral nutrition make a possible home care of patients with gastric cancer. It is necessary to make a system that supports patient life at home.

Why is the coexistence of gastric cancer and duodenal ulcer rare? Examination of factors related to both gastric cancer and duodenal ulcer.

PubMed

Ubukata, Hideyuki; Nagata, Hiroyuki; Tabuchi, Takanobu; Konishi, Satoru; Kasuga, Teruhiko; Tabuchi, Takafumi

2011-03-01

The coexistence of gastric cancer with duodenal ulcer has been found empirically to be rare, but why it is rare is difficult to explain satisfactorily. To elucidate this question, we carried out a literature review of the subject. The frequency with which the two diseases coexist is 0.1-1.7%, and the main factor associated with both gastric cancer and duodenal ulcer is Helicobacter pylori infection. However, there are marked differences between the disorders of hyperchlorhydria in duodenal ulcer, and hypochlorhydria in gastric cancer. The most acceptable view of the reason for the difference may be that the acquisition of H. pylori infection occurs mainly in childhood, so that the time of acquisition of atrophic gastritis may be the most important, and if atrophic gastritis is not acquired early, high levels of gastric acid may occur, and consequently acute antral gastritis and duodenal ulcer may occur in youth, whereas, in elderly individuals, persistent H. pylori infections and the early appearance of atrophic gastritis may be the causes of low gastric acid, and consequently gastric cancer may occur. In patients with duodenal ulcer, factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and dupA-H. pylori strains may contribute to preventing the early acquisition of atrophic gastritis, while acid-suppressive therapy and vascular endothelial growth factor and other entities may inhibit atrophic gastritis. In contrast, in gastric cancer, factors such as excessive salt intake, acid-suppressive therapy, polymorphisms of inflammatory cytokines, and the homB-H. pylori strain may contribute to the early acquisition of atrophic gastritis, while factors such as NSAIDs; fruits and vegetables; vitamins A, C, and E; and good nutrition may inhibit it.

A case report of prostate cancer metastasis to the stomach resembling undifferentiated-type early gastric cancer.

PubMed

Inagaki, Chiaki; Suzuki, Takuto; Kitagawa, Yoshiyasu; Hara, Taro; Yamaguchi, Taketo

2017-08-07

Occurrence of metastatic cancer to the stomach is rare, particularly in patients with prostate cancer. Gastric metastasis generally presents as a solitary and submucosal lesion with a central depression. We describe a case of gastric metastasis arising from prostate cancer, which is almost indistinguishable from the undifferentiated-type gastric cancer. A definitive diagnosis was not made until endoscopic resection. On performing both conventional and magnifying endoscopies, the lesion appeared to be slightly depressed and discolored area and it could not be distinguished from undifferentiated early gastric cancer. Biopsy from the lesion was negative for immunohistochemical staining of prostate-specific antigen, a sensitive and specific marker for prostate cancer. Thus, false initial diagnosis of an early primary gastric cancer was made and endoscopic submucosal dissection was performed. Pathological findings from the resected specimen aroused suspicion of a metastatic lesion. Consequently, immunostaining was performed. The lesion was positive for prostate-specific acid phosphatase and negative for prostate-specific antigen, cytokeratin 7, and cytokeratin 20. Accordingly, the final diagnosis was a metastatic gastric lesion originating from prostate cancer. In this patient, the definitive diagnosis as a metastatic lesion was difficult due to its unusual endoscopic appearance and the negative stain for prostate-specific antigen. We postulate that both of these are consequences of hormonal therapy against prostate cancer.

[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.

Transcriptomic profiling and quantitative high-throughput (qHTS) drug screening of CDH1 deficient hereditary diffuse gastric cancer (HDGC) cells identify treatment leads for familial gastric cancer.

PubMed

Chen, Ina; Mathews-Greiner, Lesley; Li, Dandan; Abisoye-Ogunniyan, Abisola; Ray, Satyajit; Bian, Yansong; Shukla, Vivek; Zhang, Xiaohu; Guha, Raj; Thomas, Craig; Gryder, Berkley; Zacharia, Athina; Beane, Joal D; Ravichandran, Sarangan; Ferrer, Marc; Rudloff, Udo

2017-05-01

Patients with hereditary diffuse gastric cancer (HDGC), a cancer predisposition syndrome associated with germline mutations of the CDH1 (E-cadherin) gene, have few effective treatment options. Despite marked differences in natural history, histopathology, and genetic profile to patients afflicted by sporadic gastric cancer, patients with HDGC receive, in large, identical systemic regimens. The lack of a robust preclinical in vitro system suitable for effective drug screening has been one of the obstacles to date which has hampered therapeutic advances in this rare disease. In order to identify therapeutic leads selective for the HDGC subtype of gastric cancer, we compared gene expression profiles and drug phenotype derived from an oncology library of 1912 compounds between gastric cancer cells established from a patient with metastatic HDGC harboring a c.1380delA CDH1 germline variant and sporadic gastric cancer cells. Unsupervised hierarchical cluster analysis shows select gene expression alterations in c.1380delA CDH1 SB.mhdgc-1 cells compared to a panel of sporadic gastric cancer cell lines with enrichment of ERK1-ERK2 (extracellular signal regulated kinase) and IP3 (inositol trisphosphate)/DAG (diacylglycerol) signaling as the top networks in c.1380delA SB.mhdgc-1 cells. Intracellular phosphatidylinositol intermediaries were increased upon direct measure in c.1380delA CDH1 SB.mhdgc-1 cells. Differential high-throughput drug screening of c.1380delA CDH1 SB.mhdgc-1 versus sporadic gastric cancer cells identified several compound classes with enriched activity in c.1380 CDH1 SB.mhdgc-1 cells including mTOR (Mammalian Target Of Rapamycin), MEK (Mitogen-Activated Protein Kinase), c-Src kinase, FAK (Focal Adhesion Kinase), PKC (Protein Kinase C), or TOPO2 (Topoisomerase II) inhibitors. Upon additional drug response testing, dual PI3K (Phosphatidylinositol 3-Kinase)/mTOR and topoisomerase 2A inhibitors displayed up to >100-fold increased activity in hereditary c.1380

Helicobacter pylori Update: Gastric Cancer, Reliable Therapy, and Possible Benefits

PubMed Central

Graham, David Y.

2015-01-01

Helicobacter pylori infection contributes to development of diverse gastric and extra-gastric diseases. The infection is necessary but not sufficient for development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, so there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk—these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma, although there are no convincing data to support the benefits of H pylori infections. PMID:25655557

Chilean Gastric Cancer Task Force

PubMed Central

Owen, Gareth I.; Pinto, Mauricio P.; Retamal, Ignacio N.; Fernádez, María F.; Cisternas, Betzabe; Mondaca, Sebastian; Sanchez, Cesar; Galindo, Hector; Nervi, Bruno; Ibañez, Carolina; Acevedo, Francisco; Madrid, Jorge; Peña, José; Bravo, Maria Loreto; Maturana, Maria Jose; Cordova-Delgado, Miguel; Romero, Diego; de la Jara, Nathaly; Torres, Javiera; Rodriguez-Fernandez, Maria; Espinoza, Manuel; Balmaceda, Carlos; Freire, Matías; Gárate-Calderón, Valentina; Crovari, Fernando; Jimenez-Fonseca, Paula; Carmona-Bayonas, Alberto; Zwenger, Ariel; Armisen, Ricardo; Corvalan, Alejandro H.; Garrido, Marcelo

2018-01-01

Abstract Gastric cancer (GC) is the world's second-leading cause of neoplastic mortality. Genetic alterations, response to treatments, and mortality rates are highly heterogeneous across different regions. Within Latin America, GC is the leading cause of cancer death in Chile, affecting 17.6 per 100,000 people and causing >3000 deaths/y. Clinical outcomes and response to “one size fits all” therapies are highly heterogeneous and thus a better stratification of patients may aid cancer treatment and response. The Gastric Cancer Task Force is a Chilean collaborative, noninterventional study that seeks to stratify gastric adenocarcinomas using clinical outcomes and genomic, epigenomic, and protein alterations in a cohort of 200 patients. Tumor samples from the Pathology Department and the Cancer Center at UC-Christus healthcare network, Pontificia Universidad Católica de Chile will be analyzed using a panel of 143 known cancer genes (Oncomine Comprehensive Assay) at the Center of Excellence in Precision Medicine in Santiago, Chile. In addition, promoter methylation for selected genes will be performed along with tissue microarray for clinically relevant proteins (e.g., PD-L1, Erb-2, VEGFR2, among others) and Helicobacter pylori and Epstein–Barr virus status. Obtained data will be correlated to 120 clinical parameters retrieve from medical records, including general patient information, cancer history, laboratory studies, comorbidity index, chemotherapy, targeted therapies, efficacy, and follow-up. The development of a clinically meaningful classification that encompasses comprehensive clinical and molecular parameters may improve patient treatment, predict clinical outcomes, aid patient selection/stratification for clinical trials and may offer insights into future preventive and/or therapeutic strategies in patients from Latin America region. Trial registration: ClinicalTrials.gov Identifier: NCT03158571, Registered on May 18, 2017. PMID:29668600

Recent advances in mass spectrometry-based proteomics of gastric cancer.

PubMed

Kang, Changwon; Lee, Yejin; Lee, J Eugene

2016-10-07

The last decade has witnessed remarkable technological advances in mass spectrometry-based proteomics. The development of proteomics techniques has enabled the reliable analysis of complex proteomes, leading to the identification and quantification of thousands of proteins in gastric cancer cells, tissues, and sera. This quantitative information has been used to profile the anomalies in gastric cancer and provide insights into the pathogenic mechanism of the disease. In this review, we mainly focus on the advances in mass spectrometry and quantitative proteomics that were achieved in the last five years and how these up-and-coming technologies are employed to track biochemical changes in gastric cancer cells. We conclude by presenting a perspective on quantitative proteomics and its future applications in the clinic and translational gastric cancer research.

Optical imaging of gastric cancer with near-infrared heptamethine carbocyanine fluorescence dyes.

PubMed

Zhao, Ningning; Zhang, Caiqin; Zhao, Yong; Bai, Bing; An, Jiaze; Zhang, Hai; Wu, Jason Boyang; Shi, Changhong

2016-08-30

Near-infrared fluorescence (NIRF) imaging agents are promising tools for noninvasive cancer imaging. Here, we explored the tumor-specific targeting ability of NIRF heptamethine carbocyanine MHI-148 dye in cultured gastric cancer cells, gastric cancer cell-derived and patient-derived tumor xenograft (PDX) models. We show that the NIRF dye specifically accumulated in tumor regions of both xenograft models, suggesting the potential utility of the dye for tumor-specific imaging and targeting in gastric cancer. We also demonstrated significant correlations between NIRF signal intensity and tumor volume in PDX models. Mechanistically, the higher cellular uptake of MHI-148 in gastric cancer cells than in normal cells was stimulated by hypoxia and activation of a group of organic anion-transporting polypeptide (OATP) genes. Importantly, this NIRF dye was not retained in inflammatory stomach tissues induced by gastric ulcer in mice. In addition, fresh clinical gastric tumor specimens, when perfused with NIR dye, exhibited increased uptake of NIR dye in situ. Together, these results show the possibility of using NIRF dyes as novel candidate agents for clinical imaging and detection of gastric cancer.

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

Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer

PubMed Central

2014-01-01

Background Protein coding genes account for only about 2% of the human genome, whereas the vast majority of transcripts are non-coding RNAs including long non-coding RNAs. A growing volume of literature has proposed that lncRNAs are important players in cancer. HOTAIR was previously shown to be an oncogene and negative prognostic factor in a variety of cancers. However, the factors that contribute to its upregulation and the interaction between HOTAIR and miRNAs are largely unknown. Methods A computational screen of HOTAIR promoter was conducted to search for transcription-factor-binding sites. HOTAIR promoter activities were examined by luciferase reporter assay. The function of the c-Myc binding site in the HOTAIR promoter region was tested by a promoter assay with nucleotide substitutions in the putative E-box. The association of c-Myc with the HOTAIR promoter in vivo was confirmed by chromatin immunoprecipitation assay and Electrophoretic mobility shift assay. A search for miRNAs with complementary base paring with HOTAIR was performed utilizing online software program. Gain and loss of function approaches were employed to investigate the expression changes of HOTAIR or miRNA-130a. The expression levels of HOTAIR, c-Myc and miRNA-130a were examined in 65 matched pairs of gallbladder cancer tissues. The effects of HOTAIR and miRNA-130a on gallbladder cancer cell invasion and proliferation was tested using in vitro cell invasion and flow cytometric assays. Results We demonstrate that HOTAIR is a direct target of c-Myc through interaction with putative c-Myc target response element (RE) in the upstream region of HOTAIR in gallbladder cancer cells. A positive correlation between c-Myc and HOTAIR mRNA levels was observed in gallbladder cancer tissues. We predicted that HOTAIR harbors a miRNA-130a binding site. Our data showed that this binding site is vital for the regulation of miRNA-130a by HOTAIR. Moreover, a negative correlation between HOTAIR and miRNA-130a was

Ion Chromatography Based Urine Amino Acid Profiling Applied for Diagnosis of Gastric Cancer

PubMed Central

Fan, Jing; Hong, Jing; Hu, Jun-Duo; Chen, Jin-Lian

2012-01-01

Aim. Amino acid metabolism in cancer patients differs from that in healthy people. In the study, we performed urine-free amino acid profile of gastric cancer at different stages and health subjects to explore potential biomarkers for diagnosing or screening gastric cancer. Methods. Forty three urine samples were collected from inpatients and healthy adults who were divided into 4 groups. Healthy adults were in group A (n = 15), early gastric cancer inpatients in group B (n = 7), and advanced gastric cancer inpatients in group C (n = 16); in addition, two healthy adults and three advanced gastric cancer inpatients were in group D (n = 5) to test models. We performed urine amino acids profile of each group by applying ion chromatography (IC) technique and analyzed urine amino acids according to chromatogram of amino acids standard solution. The data we obtained were processed with statistical analysis. A diagnostic model was constructed to discriminate gastric cancer from healthy individuals and another diagnostic model for clinical staging by principal component analysis. Differentiation performance was validated by the area under the curve (AUC) of receiver-operating characteristic (ROC) curves. Results. The urine-free amino acid profile of gastric cancer patients changed to a certain degree compared with that of healthy adults. Compared with healthy adult group, the levels of valine, isoleucine, and leucine increased (P < 0.05), but the levels of histidine and methionine decreased (P < 0.05), and aspartate decreased significantly (P < 0.01). The urine amino acid profile was also different between early and advanced gastric cancer groups. Compared with early gastric cancer, the levels of isoleucine and valine decreased in advanced gastric cancer (P < 0.05). A diagnosis model constructed for gastric cancer with AUC value of 0.936 tested by group D showed that 4 samples could coincide with it. Another diagnosis model for clinical staging with an AUC value of 0

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