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

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

Information for Patients and the Public (17 links)

Information for Health Professionals / Researchers (16 links)

See also: CDH1 Genetic Information

Helicobacter pylori and cancer (4 links)

Latest Research Publications

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

Li X, Cao B, Liu Y, et al.
Multivariate analysis of prognostic factors in 549 patients undergoing surgical treatment of gastric cancer.
Hepatogastroenterology. 2014 Mar-Apr; 61(130):535-42 [PubMed] Related Publications
BACKGROUND/AIMS: Gastric cancer is a common malignancy with high mortality rate, and surgical resection is the primary treatment.
METHODOLOGY: A retrospective analysis of patients who received surgical treatment for primary gastric cancer from January 2006 to December 2010 was performed. Cox univariate and multivariate analyses were performed to determine factors associated with decreased survival.
RESULTS: A total of 549 patients were included in the analysis (421 men and 128 women) with a mean age of 59.5 years (range, 21-81 years). Radical resection was performed in 496 patients, including D1 resection in 72 cases (14.5%), D2 resection in 380 cases (76.6%), and D3 resection in 44 cases (8.9%). The follow-up ranged from 3 to 67 months, during which 368 patients were alive or censored and 181 patients died. The overall 6-month and 1-, 3-, and 5-years survival rates were 89.8%, 80.8%, 58.9%, and 49.7% respectively. Multivariate analysis indicated that tumor size > 5 cm, increasing TNM stage, no resection, receiving perioperative blood transfusion, serum albumin <37 g/L, and not receiving postoperative comprehensive treatment (Chinese medicine, chemotherapy, immunotherapy) were associated with decreased survival.
CONCLUSIONS: Tumor size, TNM stage, extent of resection, serum albumin level, and comprehensive treatment were important prognostic factors.

Okubo M, Tahara T, Shibata T, et al.
Light blue crest and ridge/villous patterns in the uninvolved gastric antrum by magnifying NBI endoscopy correlate with serum pepsinogen and gastric cancer occurrence.
Hepatogastroenterology. 2014 Mar-Apr; 61(130):525-8 [PubMed] Related Publications
BACKGROUND/AIMS: Combining the magnifying endoscopy and the narrow-band imaging (NBI) system is an endoscopic imaging technique for the enhanced visualization of mucosal microscopic structure and capillaries of the superficial mucosal layer. Light blue crest (LBC) and, ridge/villous pattern have been thought to be suggestive signs for gastric intestinal metaplasia (IM) of magnifying NBI endoscopy. Since the IM is related to gastric cancer risk (GC), the prevalence of LBC and ridge/villous pattern in the nonneoplastic gastric antrum was examined in relation to gastric cancer (GC) risk and serological severity of gastritis.
METHODOLOGY: In 100 subjects including 13 GC patients, gastric mucosal pattern were examined using magnifying NBI. The mucosal patterns in the antrum were classified according to the presence of LBC or ridge/villous pattern. Serum pepsinogen (PG) levels were also examined.
RESULTS: The sensitivity and specificity for predicting IM was the best when LBC and ridge/villous patterns were combined (sensitivity 95.2%, specificity 98.7%). Both LBC and ridge/villous pattern showed lower serum PGI and PGI/II ratio than those without (P = 0.046, 0.0005, respectively.) In particular, PGI/II ratio was lowest in ridge/villous pattern. The LBC and ridge/villous pattern showed higher incidence of all GC and diffuse GC compared to those without (P = 0.002, 0.002, respectively).
CONCLUSIONS: LBC and ridge/villous pattern in uninvolved gastric antrum by magnifying NBI endoscopy are useful signs for predicting gastric atrophy in the entire stomach and GC risk.

Chen J, Chen LJ, Zhou HC, et al.
Prognostic value of matrix metalloproteinase-9 in gastric cancer: a meta-analysis.
Hepatogastroenterology. 2014 Mar-Apr; 61(130):518-24 [PubMed] Related Publications
BACKGROUND/AIMS: The purpose of this study was to evaluate the effect of matrix metalloproteinase-9 overexpression on clinical outcome of gastric cancer using a meta-analysis.
METHODOLOGY: Relevant studies concerning the association between Matrix metalloproteinase-9 expression and survival of patients with gastric cancer were collected from electronic databases. Hazard ratios (HRs) with 95% confidence intervals (Cls) were calculated to estimate the association. Subgroup analysis was calculated to evaluate potential sources of heterogeneity. Besides, we also assessed the relationship between Matrix metalloproteinase-9 level and relevant clinicopathological parameters by estimating the Odds ratios (ORs) with 95% Cls.
RESULTS: Ten studies with 1,478 patients were included to perform a meta-analysis of the survival results. Pooled HRs indicated that MMP-9 overexpression had a negative impact on the over survival (OS) of patients with gastric cancer (HR = 1.69, 95% Cl: 1.29-2.23, P = 0.00), without significant heterogeneity (chi2 = 14.17, I2 = 36.5%, P = 0.117). Similarly, high level of MMP-9 tended to be correlated with lymph node metastasis (OR = 1.91, 95% Cl: 1.40-2.59, P < 0.05) and presence of vascular invasion (OR = 2.64, 95% CI: 1.52-4.59, P <0.05).
CONCLUSIONS: This meta-analysis shows that Matrix metalloproteinase-9 overexpression is a poor prognostic factor in patients with gastric cancer. However, larger scale and randomized studies are needed to confirm its potential clinical value.

Related: MMP9: matrix metallopeptidase 9

Yamashita K, Sakuramoto S, Katada N, et al.
Simple prognostic indicators using macroscopic features and age in advanced gastric cancer.
Hepatogastroenterology. 2014 Mar-Apr; 61(130):512-7 [PubMed] Related Publications
BACKGROUND/AIM: Macroscopic features and age may be important prognostic factors that discriminate survival among clinical conditions requiring different therapeutic strategies of advanced gastric cancer (AGC), and this study aimed to identify their clinical relevance.
METHODOLOGY: A total of 232 AGC patients who had Surgical T2b or beyond was enrolled to identify clinical indicators, including macroscopic features in combination with age.
RESULTS: Macroscopic features were divided into 3 categories (types I/II/V, III, and IV), which included stage IV in 24%, 53%, and 72% (P < 0.0001), respectively. Macroscopic features (P < 0.0001), histological features (P = 0.025), and pathological infiltration type (P = 0.0003) were all univariate prognostic factors, as well as stage (P < 0.0001) and age (P = 0.009). However, the multivariate proportional hazards model found that macroscopic features (P = 0.0013) and age (P = 0.0091) were the only factors independent of stage (P <0.0001). Both factors clearly classified the patients into 4 groups (young type 1/II/V (group 1), elderly type I/II/V (group 2), type III and young type IV (group 3), and elderly type IV (group 4) with different prognoses.
CONCLUSIONS: Macroscopic features and age were simple indicators of prognosis in AGC. Both factors may have great potential to develop prognostic categories that effectively classify AGC into categories requiring different therapeutic strategies.

Kashihara H, Shimada M, Kurita N, et al.
Comparisons of inflammatory cytokines expressions in drain after laparoscopic versus open surgery.
Hepatogastroenterology. 2014 Mar-Apr; 61(130):379-81 [PubMed] Related Publications
BACKGROUND/AIMS: Laparoscopic surgery reduces the risk of postoperative adhesion compared with open surgery. The aim of this study was to assess the advantage of laparoscopic surgery in terms of postoperative adhesion.
METHODOLOGY: Eleven patients participated in this study (laparoscopic surgery: 6 patients, open surgery: 5 patients). Body temperature, heart rate, the duration until the first postoperative flatus and the beginning of diet were investigated on postoperative day 0, 1, 3, and 5, respectively. Serum level of WBC and CRP, PAI-1 and IFN-gamma level in the drainage tube were also measured at the same time.
RESULTS: There is no significant difference between the two groups in body temperature. The laparoscopic group revealed significantly lower WBC on POD 0 and CRP on POD 1 compared with the open group. PAI-1 was significantly lower on POD 3 and 5 in the laparoscopic group. IFN-gamma in the laparoscopic group tended to be suppressed compared with the open group.
CONCLUSIONS: Laparoscopic surgery may decrease the risk of postoperative abdominal adhesion compared with open surgery by suppressing early postoperative inflammation.

Related: Cytokines

Demir G, Unsal D, Zengin N, et al.
Analysis of resected gastric cancer in Turkish population.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):259-66 [PubMed] Related Publications
BACKGROUND/AIMS: Gastric cancer is still an important health issue in Eastern Europe and Middle East, including Turkey, although its prevalence is decreasing in the western world.
METHODOLOGY: In order to define the profiles of the patients operated with a diagnosis of gastric cancer in Turkey, a multicenter retrospective study was conducted.
RESULTS: Six hundred and forty-eight of the 840 patients with complete data in all parameters were included in the analysis. The median follow-up time was 17.16 months (range, 6-143.63 months). Mean age was 57 +/- 11.7 (19-85). There was a recurrent disease in 42% of the tumors located at cardia, corpus or antrum, and 86% of diffuse tumors (p < 0.0001). The ratio of patients with recurrent disease was greater in stage III and IV tumors There were also greater recurrence ratios in patients with node positive (pN1-3) patients than pN0 tumors, and pT3-4 tumors than pT1 or pT2 tumors. Any recurrence was found in 48% of the tumors with lymphovascular invasion, while in 39% without lymphovascular invasion (p = 0.026). A statistically significant difference was found in the recurrence status of patients with positive/dissected node ratio of < 10% and > or = 10% (p < 0.0001).
CONCLUSIONS: Gastric cancer cases in Turkey are seen at a younger age, and at a higher stage. Proximal gastric cancer is seen much less than the western series. Prognostic significance of lymphovascular invasion in both univariate, and multivariate analyses is noteworthy.

Yun L, Bin Z, Guangqi G, et al.
Clinical significance in combined detection of serum pepsinogen I, pepsinogen II and carbohydrate antigen 242 in gastric cancer.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):255-8 [PubMed] Related Publications
BACKGROUND/AIMS: To explore the diagnosis value and clinical significance of combined detection of serum pepsinogen I (PG I), pepsinogen II (PG II), PG I/II and CA242 in patients with stomach diseases.
METHODOLOGY: Serum PG I, PG II and CA242 were detected with time-resolved fluoroimmunoassay (TRFIA) method. Serum levers of the four markers in gastric carcinoma were compared with that in chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer and normal controls. The four indices were analyzed to judge their diagnosis value and the relationship with the biology behavior of gastric carcinoma.
RESULTS: The serum concentration of PG I in gastric carcinoma and in chronic atrophic gastritis were remarkably lower than that in controls (P < 0.05). The serum concentration of CA242 in gastric carcinoma was significantly higher than that in controls (P < 0.05).
CONCLUSIONS: To detect the levers of serum PG I, PG II, PG I/II would help to judge the metastasis and prognosis of gastric carcinoma. Combined detection of the four indices could increase the positive rate of diagnosis in gastric carcinoma.

Sasaki K, Fujiwara Y, Kishi K, et al.
Pathological findings of gastric mucosa in patients with gastric remnant cancer.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):251-4 [PubMed] Related Publications
BACKGROUND/AIMS: The mechanism of remnant gastric cancer development has not yet been well established. In this study, we compared the background gastric mucosa of remnant gastric cancer with that of upper lesion-restricted gastric cancer to determine the difference in the pathogenesis of naive gastric cancer and remnant gastric cancer.
METHODOLOGY: Twenty-five patients with gastric remnant cancer after distal gastrectomy and a control group of 29 patients with naive gastric cancer restricted to the upper part of the stomach who underwent gastrectomy were enrolled in this study. We evaluated the gastric mucosa adjacent to cancerous tissues using the updated Sydney score system.
RESULTS: The surrounding gastric mucosa in the remnant gastric cancer group was significantly less atrophic than that of the group with gastric cancer restricted to the upper part of the stomach. In remnant gastric cancer, patients who underwent Billroth II (B-II) reconstruction at first gastrectomy developed cancer at the anastomotic site more frequently than those with Billroth I (B-I) reconstruction.
CONCLUSIONS: The surrounding gastric mucosa was significantly less atrophic in remnant gastric cancer than naïve gastric cancer, which indicates that remnant gastric cancer might possess a different pathogenesis.

Hu WQ, Wang LW, Yuan JP, et al.
High expression of transform growth factor beta 1 in gastric cancer confers worse outcome: results of a cohort study on 184 patients.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):245-50 [PubMed] Related Publications
BACKGROUND/AIMS: Transform growth factors beta (TGFbeta) plays different roles at different stages of tumor development. TGFbeta1 is one isoform of TGFbeta, with complex secretion mechanism and bidirectional functions. This study was to investigate TGFbeta1 expression and its clinical significance in different clinicopathological subgroups of gastric cancer (GC) patients.
METHODOLOGY: Tumor and peritumoral tissues from 184 GC patients were constructed into three tumor tissue microarrays. The expression of TGFbeta1 was analyzed by immunohistochemistry methods.
RESULTS: TGFbeta1 was mainly expressed in the cytoplasm and membrane of GC cells. Low TGFbeta1 expression was observed in 82 (44.6%) tumor and 28 (68.3%) peritumoral tissues, and high expression was observed in 102 (55.4%) tumor and 13 (31.7%) peritumoral tissues. TGFbeta1 expression was significantly higher in tumor than peritumoral tissues (chi2 = 7.554, P = 0.006). The high expression of TGFbeta1 was related to worse overall survival (OS) (P = 0.040). TGFbeta1 expression was higher in the old and intestinal type GC than in the young (P = 0.017) and in diffuse type GC (P = 0.015), respectively. Patients with high TGFbeta1 expression had a worse survival in young people, female, diffuse type GC, poor differentiation, and lymph nodes metastasis. Multivariate Cox proportional hazards analysis showed that age, pathological grading, serosal invasion and TGFbeta1 expression were independent risk factors.
CONCLUSIONS: High TGFbeta1 expression may indicate poor prognosis of GC patients and warrant more active treatment against TGFbeta1.

Related: TGFB1

Nishizawa M, Seshimo A, Miyake K, et al.
Usefulness of the TRC method in the peritoneal washing cytology for gastric cancer.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):240-4 [PubMed] Related Publications
BACKGROUND: Peritoneal dissemination from gastric cancer is the most frequent metastasis of advanced gastric cancer. Detection of cancer micrometastasis is required for improvement of cancer therapy. A method that can detect micrometastases more sensitively is desired. Against this background, for the purposes of making the genetic diagnosis of micrometastasis simple and rapid, TRC (transcription reverse transcription concerted reaction) was developed.
METHODOLOGY: 69 patients with gastric cancer in those diagnosed with deeper than mp. At the time of surgery, peritoneal washing with saline was extracted. Having extracted the RNA therein, It was blended with a reagent responsive to CEAmRNA and was put into TRC. The cytology and TRC were compared and studied.
RESULTS: The concordance rate between TRC and cytology was K=0.6552. The patients whom there was a discrepancy between the cytology and TRC are clinically validate the TRC results. In the study of prognosis, TRC obtained a sensitivity of 90.9% and a specificity of 98.3%.
CONCLUSION: The measurement of CEAmRNA in peritoneal washing specimens by the TRC method is superior to Cytology. That is also equal to or superior to the RT-PCR method with respect to sensitivity and specificity, and superior with respect to simplicity and rapidity.

Xu Q, Gu L, Jiang C, et al.
The selection of surgical treatment for gastric cancer patients with cirrhosis and hypersplenism.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):232-5 [PubMed] Related Publications
BACKGROUND/AIMS: This study is to find the changes of hypersplenism, the leukocyte, platelets count, blood loss and operative time, hospitalization days in gastric cancer patients with cirrhosis and hypersplenism after splenectomy or splenic artery ligation.
METHODOLOGY: 32 gastric cancer patients with cirrhosis and hypersplenism were divided into two groups performed radical gastrectomy combined with splenectomy (Group A, n = 17) or splenic artery ligation (Group B, n = 15), 16 gastric cancer patients performed radical gastrectomy were selected as control group (Group C). Then, statistical analyzed.
RESULTS: There were no significant differences of the leukocyteand platelets between Group A and B (p > 0.05), but significant compared with Group C (p < 0.01). After 6 chemotherapy, the differences of the leukocyteand platelets were obvious between Group A and C (p < 0.05), but not between Group B and C (p > 0.05). There were significant differences on the grading of hyperhepatia between Group A and B. Except the operative time of Group B and C (p > 0.05), there were significant differences on the blood loss, the operative time and hospitalization days among three groups (p < 0.05).
CONCLUSIONS: The splenic artery ligation method was much more rational than splenectomy and it was preferred for the gastric cancer patients with cirrhosis and hypersplenism.

Related: Fluorouracil Leucovorin

Yajima H, Omura N, Matai K, et al.
Clinicopathological features of CA19-9-producing gastric cancer.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):221-5 [PubMed] Related Publications
BACKGROUND/AIMS: The aims of this study were to define CA19-9-producing gastric cancer and investigate its clinicopathological features.
METHODOLOGY: Twenty-three patients showing high preoperative serum CA19-9 levels (> or = 38 U/mL) were enrolled in this retrospective cohort study. The CA19-9 cut-off level was determined on the basis of receiver operating characteristic analysis of CA19-9 levels obtained from patients having survived for 3 years after surgery. Patients in whom the CA19-9 level was the cut-off level or higher were defined as having CA19-9-producing gastric cancer (Group A), and their clinicopathological features were compared with those of patients showing CA19-9 levels less than the cut-off level (Group B).
RESULTS: The preoperative serum CA19-9 cut-off level was set at 77 U/mL. In Group A, lymph node metastasis was seen in all 11 patients, with the incidence being higher than that in Group B (p <0.001). The number of patients with stage III or greater disease was 10 in Group A, compared with only 3 in Group B (p < 0.001). The independent prognostic factors were preoperative serum CA19-9 levels, venous invasion and tumor stage.
CONCLUSIONS: CA19-9-producing gastric cancer is a type of gastric cancer with poor prognosis and characterized by preoperative serum CA19-9 > or = 77 U/mL.

Alldinger I, Schmitt MM, Dreesbach J, Knoefel WT
Endoscopic treatment of anastomotic leakage after esophagectomy or gastrectomy for carcinoma with self-expanding removable stents.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):111-4 [PubMed] Related Publications
BACKGROUND/AIMS: Anastomotic leakage is a feared complication after gastrectomy and esophagectomy. We report our experience in the treatment with endoscopic stent placement.
METHODOLOGY: Seventeen patients with anastomotic leakage after resection of a malignant tumor of the stomach or the distal esophagus have been long-term followed-up.
RESULTS: In 10 patients the implanted stent did successfully close the leakage in the first attempt. In 3 out of 7 patients with unsuccessfully sealed leakage a stent-in-stent-manoeuvre did successfully seal the leakage. We had no major complications upon implantation of the stents. We did have no recurrence of a once sealed leakage.
CONCLUSIONS: Endoscopic stent placement is a safe procedure in the treatment of anastomotic leakage after gastrectomy and esophagectomy. It should be performed in any clinically relevant leakage if possible. In cases where stent placement is not successful at first, correction of position, stent replacement or a stent-in-stent manoeuvre can be performed, with promising results.

Related: Cancer of the Esophagus Esophageal Cancer

Park JY, Kim YW, Eom BW, et al.
Unique patterns and proper management of postgastrectomy bleeding in patients with gastric cancer.
Surgery. 2014; 155(6):1023-9 [PubMed] Related Publications
BACKGROUND: Bleeding after gastrectomy is a less frequent, but fatal complication. Because the pathophysiology and clinical manifestations differ considerably across cases, the exact outcome of postoperative bleeding is unclear. This study aimed to improve management practices for postgastrectomy bleeding by the analysis of risk factors and clinical patterns.
METHODS: From January 2001 to December 2010, 5,739 patients underwent gastrectomy for gastric cancer at the National Cancer Center, Korea. Clinical data from patients with postoperative bleeding were obtained from a prospectively established database, and risk factors for bleeding were analyzed using multivariate binary logistic regression.
RESULTS: Incidence of the postoperative bleeding was 0.8% (n = 48) and the subsequent mortality rate was 10% (5/48). Majority of anastomotic bleeding occurred early within 1 day of the operation (5/7; 71%). It was successfully managed with conservative treatment in 3 patients, endoscopic intervention in 2, and relaparotomy in 2. Arterial bleeding occurred in 24 patients, with the main site being the splenic artery (11/24; 46%), and mostly manifested in the delayed period (median, 12 days). Fifteen of them underwent radiologic intervention, and 4 of these patients were referred for operation eventually. The other 9 patients underwent relaparotomy as first-line treatment. Independent risk factors for the bleeding were male (hazard ratio [HR] 2.253; 95% CI, 1.079-4.704), comorbidity (HR, 2.709; 95% CI, 1.440-5.095), previous abdominal operation (HR, 2.785; 95% CI, 1.322-5.867), and palliative surgery (HR, 4.142; 95% CI, 1.443-11.889).
CONCLUSION: Postgastrectomy bleeding can be managed properly considering its origin, severity, onset, and the risk factors.

Ford AC, Forman D, Hunt RH, et al.
Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials.
BMJ. 2014; 348:g3174 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals.
DESIGN: Systematic review and meta-analysis of randomised controlled trials.
DATA SOURCES: Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥ 2 years.
MAIN OUTCOME MEASURES: Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals.
RESULTS: The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I(2)=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women.
CONCLUSIONS: These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations.

Li C, Zhao W, Liu B, et al.
Cytotoxicity of ultrafine monodispersed nanoceria on human gastric cancer cells.
J Biomed Nanotechnol. 2014; 10(7):1231-41 [PubMed] Related Publications
The safety and toxicity of CeO2 nanoparticles (nanoceria) are of growing concern due to their potential applications in biological and medical fields based on the radical scavenging and UV-filtering properties. In this paper, the ultrafine monodisperse (2-5 nm) water-insoluble (CeO2-P) and water-soluble nanoceria modified with various functional groups of dextran (CeO2-dextran), polyacrylic acid (CeO2-PAA) and ethylenediamine (CeO2-EDA) on surface were synthesized via alkaline-based precipitation and inverse microemulsion methods. The cell uptaking, oxidative stress and cytotoxicity of these nanoceria on human gastric cancer cell line (BGC-803) were systematically investigated. It is found that the cell uptaking of nanoceria is largely relied on the function groups on its surfaces and followed the order: CeO2-P > CeO2-EDA > CeO2-dextran > CeO2-PAA. Moreover, the oxidative stress of BGC-803 cells is obviously affected by the antioxidant capacity of nanoceria determined by Ce3+/Ce4+ ratio, which eventually causes the cell viability variable once the nanoceria entered into BGC-803 cells. In addition, the cell viability is also closely correlated with the concentration and surface characteristics of nanoceria. The cytotoxicity of nanoceria on BGC-803 cells is largely dependent on its surface functional groups. Our work may provide guidance on the cytotoxicity of ultrafine monodisperse nanoceria for their uses in biological and medical fields.

Fu HL, Ma Y, Lu LG, et al.
TET1 exerts its tumor suppressor function by interacting with p53-EZH2 pathway in gastric cancer.
J Biomed Nanotechnol. 2014; 10(7):1217-30 [PubMed] Related Publications
TET1 protein is reported to suppress cancer invasion and metastasis in prostate and breast cancer while EZH2, a polycomb group protein, has been identified as an oncogene in many types of cancers including gastric cancer. Here we report that there is an inverse relation of the expression pattern of TET1 and EZH2 in both normal gastric mucosa and gastric cancer. In gastric mucosa, EZH2 is selectively expressed in the proliferating neck cells while TET1 and 5-hydroxymethyl-cytosine (5-hmc) exhibit very low expression in the neck cells. In contrast, TET1 and 5-hmc expression is high in gastric glandular epithelium while EZH2 expression is absent in this cell population. On the other hand, in proliferating Ki67-positive gastric cancer cells, EZH2 is highly expressed while TET1 and 5-hmc expression is significantly down-regulated. When the mouse homologue of human TET1 protein Tet1 is overexpressed in a gastric cancer cell line MGC-803, we observed the dramatically down-regulation of EZH2 in one-third of the Tet1 overexpressed cells. In addition, Tet1 overexpressing cells also lost the H3K27 trimethylation mark and the cell proliferation protein Ki67. Furthermore, Tet1 overexpression induced p53 tumor suppressor protein. The increase of p53 protein level is accompanied by the phosphorylation of p53 by activated DNA-PK. Together, these results suggested a mechanism by which TET1 suppresses cancer formation by coupling DNA demethylation with DNA-PK activation of p53 and suppression of oncogenic protein EZH2. Conversely, loss of TET1 and 5-hmc expression might contribute to EZH2 up-regulation during gastric cancer development.

Related: MKI67 Signal Transduction TP53 TET1 TET2 gene

An X, Wang F, Shao Q, et al.
MET amplification is not rare and predicts unfavorable clinical outcomes in patients with recurrent/metastatic gastric cancer after chemotherapy.
Cancer. 2014; 120(5):675-82 [PubMed] Related Publications
BACKGROUND: Several large studies have reported an extremely low incidence of MET gene amplification (GA) in patients with radically resected gastric cancer. This study was conducted to evaluate the prevalence and prognostic role of MET in patients with recurrent=metastatic gastric cancer who received chemotherapy.
METHODS: MET GA and protein expression of recurrent=metastatic gastric cancer samples were evaluated by fluorescence in situ hybridization and immunohistochemistry (IHC), respectively.
RESULTS: This retrospective study included 232 patients with recurrent=metastatic gastric cancer. MET GA and strong protein expression(IHC31) were observed in 8.3% (19 of 230 samples) and 9.6% (22 of 229 samples) of samples, respectively. A significant correlation was observed between MET GA and protein expression (r = 0.378; P<.001). MET GA was correlated with poor performance status(P<.001) and poorly differentiated tumors (P=.0015). Both MET GA and IHC 31 expression were associated with a substantially shorter median overall survival (OS) and progression-free survival (PFS). The median OS and PFS for patients with MET GA versus those without MET GA were 5.7 months versus 15.5 months (P<.001) and 3.6 months versus 6.9 months (P<.001), respectively. The median OS and PFS for patients with MET IHC 31 expression versus IHC 0 to 21 expression were 6.3 months versus 15.1 months(P<.001) and 3.6 months versus 7.0 months (P<.001), respectively.
CONCLUSIONS: In patients with recurrent=metastatic gastric cancer,MET amplification and strong protein expression are not rare and appear to be significantly associated with unfavorable clinical outcomes.

Related: FISH

Smith RC, Creighton N, Lord RV, et al.
Survival, mortality and morbidity outcomes after oesophagogastric cancer surgery in New South Wales, 2001-2008.
Med J Aust. 2014; 200(7):408-13 [PubMed] Related Publications
OBJECTIVES: To examine the relationship between hospital volume and patient outcomes for New South Wales hospitals performing oesophagectomy and gastrectomy for oesophagogastric cancer.
DESIGN, SETTING AND PATIENTS: A retrospective, population-based cohort study of NSW residents diagnosed with a new case of invasive oesophageal or gastric cancer who underwent oesophagectomy or gastrectomy between 2001 and 2008 in NSW hospitals using linked de-identified data from the NSW Central Cancer Registry, the National Death Index and the NSW Admitted Patient Data Collection. A higher-volume hospital was defined as one performing > 6 relevant procedures per year.
MAIN OUTCOME MEASURES: Odds ratios for > 21-day length of stay, 28-day unplanned readmission, 30-day mortality and 90-day mortality, and hazard ratios (HRs) for 5-year absolute and conditional survival.
RESULTS: Oesophagectomy (908 patients) and gastrectomy (1621 patients) were undertaken in 42 and 84 hospitals, respectively, between 2001 and 2008. Median annual hospital volume ranged from 2 to 4 for oesophagectomies and ranged from 2 to 3 for gastrectomies. Controlling for known confounders, no associations between hospital volume and > 21-day length of stay and 28-day unplanned readmission were found. Overall 30-day mortality was 4.1% and 4.4% for oesophagectomy and gastrectomy, respectively. Five-year absolute survival was significantly better for patients who underwent oesophagectomy in higher-volume hospitals (adjusted HR for lower-volume hospitals, 1.28 [95% CI, 1.10-1.49]; P = 0.002) and for those with localised gastric cancer who underwent gastrectomy in higher-volume hospitals (adjusted HR for lower-volume hospitals, 1.83 [95% CI, 1.28-2.61]; P = 0.001).
CONCLUSIONS: These data support initial surgery for oesophagogastric cancer in higher-volume hospitals.

Related: Cancer of the Esophagus Esophageal Cancer

Kim BS, Oh ST, Yook JH, Kim BS
Signet ring cell type and other histologic types: differing clinical course and prognosis in T1 gastric cancer.
Surgery. 2014; 155(6):1030-5 [PubMed] Related Publications
BACKGROUND: The behavior of early stage signet ring cell carcinoma (SRC) is controversial. The purpose of this study was to clarify the behavior of early gastric SRC.
METHODS: We retrospectively analyzed data from 2,085 patients who had undergone curative gastrectomy for early gastric cancer between 1989 and 2000. Clinicopathologic outcomes and prognoses were evaluated, and we investigated whether these variables were correlated with histopathologic type.
RESULTS: Patients with early gastric SRC were younger and had a greater proportion of females than other histologic types. Lymph node metastasis was the only independent prognostic factor for both mucosal and submucosal forms of SRC. Mucosal SRC had a similar rate of lymph node metastasis to poorly differentiated (PD) tubular adenocarcinoma (TUB), and a higher rate than well-differentiated (WD) or moderately differentiated (MD)-TUB. However, its submucosal form had a similar rate of lymph node metastasis to WD-TUB, and a lower rate than MD- or PD-TUB. There was no difference in tumor recurrence or disease-related death according to histopathologic type or depth of invasion.
CONCLUSION: In mucosal gastric cancer, SRC has an unfavorable risk factor of lymph node metastasis than that of others and should not be considered for endoscopic resection. In submucosal gastric cancer, SRC is a more favorable risk factor of lymph node metastasis than that of other histologic types.

Mehmedović A, Mesihović R, Saray A, Vanis N
Gastric cancer staging: EUS and CT.
Med Arch. 2014; 68(1):34-6 [PubMed] Related Publications
INTRODUCTION: Gastric cancer is the fourth most common cancer and the second leading cause of death from cancer. Only complete resection of all gross disease with negative microscopic margins (R0 resection) provides a long-term survival benefit, and the overall 5-year relative survival rate is approximately 20%. To improve survival and quality of life, new therapeutic approaches have been introduced.
MATERIAL AND METHODS: A total of 277 patients (171 men, 106 women) were included in this analysis. The results from the preoperative EUS and MDCT were compared to the postoperative pathological findings. A radial scanning ultrasonic endoscope was used. In patients with early gastric cancer, especially in cases confined to mucosa, endoscopic resection is performed to avoid unnecessary surgical procedures. To achieve R0 resection for locally-advanced gastric cancer, neoadjuvant treatments have been investigated.
RESULTS AND DISCUSSION: Laparoscopic surgery has been shown to improve quality of life for both early and locally advanced gastric cancer. Endoscopic ultrasonography (EUS), which is considered to be the most precise method for locoregional staging, was commonly used for differentiating mucosal lesions from submucosal lesions. By contrast, computed tomography (CT) was used to detect the presence of distant metastasis. The difference in accuracy between the < or = 20-mm group and other groups was statistically significant for both EUS and MDCT (P = 0.026 and P = 0.044, respectively).
CONCLUSION: However, recent technological advances with the helical and multi-detector scanners have provided better CT performance.

Adams HL, Jaunoo SS
Clinical significance of incidental findings on staging positron emission tomography for oesophagogastric malignancies.
Ann R Coll Surg Engl. 2014; 96(3):207-10 [PubMed] Related Publications
INTRODUCTION: The aim of this retrospective study was to determine the clinical significance of incidental findings detected on positron emission tomography (PET) in patients undergoing staging of oesophagogastric malignancies.
METHODS: Patients with oesophagogastric malignancies who underwent PET between June 2007 and May 2012 were included in the study. PET was performed according to hospital protocol. All imaging was interpreted by two consultant radiologists in nuclear medicine. Incidental findings that were unrelated to the primary malignancy were recorded and patients were recommended to have further investigations (imaging, endoscopy and biopsy).
RESULTS: Overall, 333 patients (240 male, 93 female; mean age: 67 years) with upper gastrointestinal malignancies were eligible for inclusion in the study. Eighty-nine of these patients had PET demonstrating one or more incidental findings. Two patients were found to have a second primary malignancy. One patient had a distant metastasis of his primary cancer and six patients had a premalignant lesion.
CONCLUSIONS: In this study, incidental findings were discovered in 26.7% of patients with known oesophagogastric cancer. A second primary cancer or premalignant lesion was found in 8.4% of patients with incidental findings. Patients with these findings should be investigated to rule out further malignancy. There were a high proportion of false positive results in our study. It is recommended that each patient is considered on an individual basis and assessed with simultaneous PET and computed tomography.

Related: Cancer of the Esophagus Esophageal Cancer

Oshima T, Yoshihara K, Aoyama T, et al.
Relation of INHBA gene expression to outcomes in gastric cancer after curative surgery.
Anticancer Res. 2014; 34(5):2303-9 [PubMed] Related Publications
Inhibin-βA (INHBA), a ligand belonging to the transforming growth factor-β superfamily, is associated with cell proliferation in cancer. We studied the relations of INHBA gene expression to clinicopathological factors and outcomes in 168 patients with gastric cancer who underwent curative surgery. Relative INHBA gene expression was measured in surgical specimens of cancer tissue and adjacent normal mucosa by quantitative real-time, reverse-transcription polymerase chain reaction. INHBA expression levels were significantly higher in cancer tissue than in adjacent normal mucosa and were related to TNM stage and venous invasion. High INHBA gene expression was associated with significantly poorer 5-year overall survival than was low expression. On multivariate analysis, INHBA gene expression was an independent prognostic factor. Overexpression of the INHBA gene is considered a useful independent predictor of outcomes in patients with gastric cancer after curative surgery.

Lin CH, Lin CC, Tsai CW, et al.
Association of caveolin-1 genotypes with gastric cancer in Taiwan.
Anticancer Res. 2014; 34(5):2263-7 [PubMed] Related Publications
Gastric cancer is one of the leading causes of tumor-related death worldwide, for which the prevalence and mortality rates are very high in developed countries. Caveolin-1 (Cav-1) is the main protein in the caveolin family and plays a role in tumorigenesis signaling. The contribution of CAV1 genetic variants to gastric cancer is still largely unknown. In the present study, we aimed to investigate the role of CAV1 genotypes in gastric cancer risk. We recruited 358 gastric patients and 358 cancer-free controls for CAV1 genotyping analysis. Six single-nucleotide polymorphisms (SNPs) of CAV1, C521A (rs1997623), G14713A (rs3807987), G21985A (12672038), T28608A (rs3757733), T29107A (rs7804372), and G32124A (rs3807992), were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. There was a significant difference between the gastric cancer and control groups in the genotypic frequency distribution of the CAV1 G14713A genotypes (p=1.24*10(-5)), with those carrying the A allele having a higher risk for gastric cancer compared to those with the GG genotype (p=0.0001). Our findings suggested that CAV1 genotype may determine the individual susceptibility to gastric cancer, and that the CAV1 G14713A genotype may serve as a novel biomarker for early detection and prediction of gastric cancer.

Cheng TY, Wu MS, Lin JT, et al.
Formyl Peptide receptor 1 expression is associated with tumor progression and survival in gastric cancer.
Anticancer Res. 2014; 34(5):2223-9 [PubMed] Related Publications
BACKGROUND: Formyl peptide receptor 1 (FPR1) as a regulator of innate inflammatory response has been implicated in tumor progression of gliomas. The purpose of the present study was to evaluate the prognostic significance and the ligand-receptor interaction of FPR1 in gastric cancer (GC).
PATIENTS AND METHODS: FPR1 was immunohistochemically-analyzed in tissue sections originating from 116 GC patients. Reverse transcription-polymerase chain reaction (RT-PCR) was used for the assessment of interaction between FPR1 and the FPR1 ligand annexin A1 (AnxA1) in GC cells.
RESULTS: High FPR1 expression was significantly associated with stage IV disease, submucosal invasion, serosal invasion, and clinical outcome of GC. Multivariate analysis showed that high FPR1 expression was an independent risk factor of poor overall survival in GC patients. FPR1 expression increased significantly when AnxA1 overexpression was present in GC cells. A positive feedback regulation of FPR1 was involved in the AnxA1-FPR1 signal transduction.
CONCLUSION: FPR1 expression may be used as a novel indicator to predict outcome in GC patients after gastrectomy.

Jia S, Jia Y, Weeks HP, et al.
Down-regulation of WAVE2, WASP family verprolin-homologous protein 2, in gastric cancer indicates lymph node metastasis and cell migration.
Anticancer Res. 2014; 34(5):2185-94 [PubMed] Related Publications
BACKGROUND: WAVE2 plays a crucial role in actin polymerisation and cell migration. We aimed to investigate the expression and cellular functions of WAVE2 in human gastric cancer (GC).
MATERIALS AND METHODS: The level of WAVE2 was determined using quantitative PCR (Q-PCR) in a cohort of human gastric tissues. Expression of WAVE2, ARP2, NWASP, ROCK1 and ROCK2 was examined using RT-PCR in paired tissues. WAVE2 and ARP2 protein co-expression was examined. Anti-WAVE2 transgene ribozymes were constructed and transiently transfected into human GC cells.
RESULTS: Down-regulation of WAVE2 expression in GC was significantly correlated with lymph node metastasis. WAVE2 was positively correlated with E-cadherin and negatively with TWIST. Immunohistochemically, WAVE2 and ARP2 were not co-expressed in serial mirror sections. In vitro, WAVE2 knockdown was shown to increase cell motility, whilst ROCK inhibitor treatment reduced this effect in HGC27 cells.
CONCLUSION: WAVE2 is down-regulated in GC and loses its metastatic role in GC. Knockdown of WAVE2 could increase metastatic potential by promoting the growth, invasiveness, motility, adhesiveness and suppressing EMT (epithelial-mesenchymal transition) of GC cells.

Lasithiotakis K, Antoniou SA, Antoniou GA, et al.
Gastrectomy for stage IV gastric cancer. a systematic review and meta-analysis.
Anticancer Res. 2014; 34(5):2079-85 [PubMed] Related Publications
AIM: Gastrectomy as a primary treatment for patients with metastatic gastric cancer (M1) is highly controversial. Herein, a review of the literature was undertaken with the aim of assessing evidence regarding associated morbidity and mortality, overall survival, palliation and quality of life.
MATERIALS AND METHODS: A systematic review of the literature from 1980 to 2013 was undertaken to identify relevant studies. Outcome data were pooled, and combined overall effect sizes were calculated using fixed or random effects models. The search identified 19 non-randomized studies reporting on 2,911 patients.
RESULTS: Overall postoperative mortality and morbidity were 14% and 27% and were higher in Western than in Asian patients. In studies published during the past decade postoperative mortality was less than 5%. The weighted 1- and 2-year overall survival rates were 38% and 17%, and were twice as high in Asian versus Western patients. In the meta-analysis, the 1-year overall survival was significantly higher in patients undergoing gastrectomy versus conservative (odds ratio (OR)=4.9, 95% confidence interval (CI)=3.2 to 7.5, p<0.0001) or gastrectomy versus non-resectional treatment (OR=2.6, 95% CI=1.7 to 4.3, p<0.0001). Studies reporting on quality of life and palliation indicate a possible benefit of such palliative gastrectomy.
CONCLUSION: A possible benefit of gastrectomy compared to non-resectional treatment for stage IV gastric cancer in terms of survival and palliation was evident but has to be cautiously interpreted due to potential sources of bias of retrospective non-randomized studies. Several questions regarding the optimal management of these patients remain unanswered and require a properly-designed randomized trial.

Gallo P, Gentilucci UV, Taffon C, et al.
A challenging alfa-fetoprotein in a cirrhotic patient.
Acta Gastroenterol Belg. 2014; 77(1):66-7 [PubMed] Related Publications
A 57-year-old Italian man was admitted to our Hospital for investigation of a progressively raising alfa-fetoprotein (AFP) on the background of chronic hepatitis B infection. At abdominal imaging,liver morphology was suspected for advanced fibrosis but without any focal lesion. Clinical and ultrasonographic examinations were negative for testicular masses. When the patient was screened for gastroesophageal varices, upper intestinal endoscopy did not show signs of portal hypertension, while it revealed a gastric lesion which was histologically characterized as hepatoid adenocarcinoma of the stomach (HAS), with strong immunohistochemical positivity for AFP. The patient underwent subtotal gastrectomy and AFP fell within the normal range. This is a very rare case in which AFP-producing gastric cancer (AFPPGC), in the form of HAS, presented in a patient with chronic liver disease. Physicians should be particularly aware of AFPPGC when following patients with liver disorders due to the common use of AFP in this setting.

Related: Liver Cancer

Wang Q, Liu P, Sun Y, et al.
Pluronic-poly[alpha-(4-aminobutyl)-1-glycolic acid] polymeric micelle-like nanoparticles as carrier for drug delivery.
J Nanosci Nanotechnol. 2014; 14(7):4843-50 [PubMed] Related Publications
Pluronic-poly[alpha-(4-aminobutyl)-1-glycolic acid] (Pluronic-PAGA) with different types of Pluronic, the different molecule weight of PAGA, and the different molar ratios of Pluronic to PAGA were synthesized. These materials were bio-degradable, amphiphilic, could be degraded into non-toxic small molecules and could be used to carry drugs. 5-Fluorouracil (5-Fu) loaded Pluronic-PAGA micelle-like nanoparticles (5-Fu loaded P-PAGA NPs) were prepared by a simple self-assembly method, and characterized by dynamic light scattering, transmission electron microscope. The degradation and release characteristics have also been studied in this paper. With the time passing, the 5-Fu loaded P-PAGA NPs degraded into smaller ones with the similar characteristics of the original NPs. Both the types of Pluronic and the molecule weight of the PAGA affected the releasing progresses. It was found that 5-Fu loaded P-PAGA NPs exhibited high growth inhibitory effect on human gastric cancer cells by MTT assay. The cellular uptake of Rhodamine B loaded P-PAGA NPs was higher than free Rhodamine B. This study suggested that the Pluronic-PAGA with acceptable drug entrapment efficiencies, drug loading efficiencies and tunable release profiles could offer an alternative carrier for 5-Fu delivery and have the potential for the delivery of other anti-tumour drug.

Related: Fluorouracil

Gu L, Liu L, Zhong L, et al.
Cthrc1 overexpression is an independent prognostic marker in gastric cancer.
Hum Pathol. 2014; 45(5):1031-8 [PubMed] Related Publications
Collagen triple helix repeat containing 1 (CTHRC1) was identified as a novel gene expressed in the adventitia and neointima on arterial injury and was found to be overexpressed in several malignant tumors, such as breast cancer and malignant melanoma. However, the expression of Cthrc1 and its role in gastric cancer progression remain unknown. We investigated the expression of the Cthrc1 protein by immunohistochemistry in 30 normal tissues from the control subjects and 166 gastric carcinomas and analyzed its correlation with various clinicopathological features, including patient outcome. Cthrc1 immunoreactivity was overexpressed in gastric carcinoma cases compared with normal tissues (P < .001). High Cthrc1 expression was found in 108 (65.06%) of these 166 carcinomas and was positively correlated with the American Joint Committee on Cancer stage classification, depth of gastric wall invasion, lymph node metastasis, lymphovascular space involvement, and recurrence but not with age, tumor site, and carcinoembryonic antigen level. Patients with high Cthrc1 expression had significantly poorer overall survival and disease-free survival compared with patients with low expression of Cthrc1 (P = .001 and P = .002, respectively). Multivariate analysis showed that high Cthrc1 expression was an independent prognostic factor for both overall survival and disease-free survival of patients with gastric carcinoma (both P = .005). These results showed that high Cthrc1 expression was associated with progression and prognosis of gastric carcinoma.

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