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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Helicobacter pylori and cancer
Gastrointestinal System Cancers
Latest Research Publications

Information for Patients and the Public (16 links)


Information for Health Professionals / Researchers (16 links)

See also: CDH1 Genetic Information

Helicobacter pylori and cancer (4 links)

Latest Research Publications

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

Kodera Y
Gastric cancer with minimal peritoneal metastasis: is this a sign to give up or to treat more aggressively?
Nagoya J Med Sci. 2013; 75(1-2):3-10 [PubMed]
Peritoneal metastasis from gastric cancer is often undetectable by routine imaging studies. Even a microscopic metastasis detected only by cytologic examination of the peritoneal washes denotes a dismal prognosis, and surgery is ruled out as futile for patients who turn out to be cytology-positive by staging laparoscopy. On the other hand, recent developments in cancer chemotherapy have improved the outcome of the cytology-positive population to the point where a certain proportion of these patients survive for 5 years through a straightforward strategy of radical surgery followed by chemotherapy. Thus, there is certainly a role for surgeons in patients with minimal peritoneal metastasis, both in clinical practice and in clinical trials where multimodal treatment strategies including surgery are to be explored. Even in this category of patients, surgery in combination with various types of chemotherapy remains the only hope for a cure.


Li X, Chu J, Sun C, et al.
Sixty-four-slice computed tomography angiography of perigastric veins with image fusion.
J Comput Assist Tomogr. 2013 Mar-Apr; 37(2):165-70 [PubMed]
OBJECTIVE: The objective of this study was to assess the efficacy and clinical value of 64-slice computed tomography angiography (CTA) with image fusion for demonstrating the perigastric venous anatomy.
METHODS: Twenty-six patients with gastric cancer underwent abdominal CTA examinations. Computed tomography angiography of stomach and perigastric veins and arteries were reconstructed and fused using volume-rendering technique. The inflow and courses of perigastric veins as well as the spatial relationship among the perigastric veins, arteries, and stomach were compared with surgery.
RESULTS: Compared with surgical findings, the visualization rate of the 7 perigastric veins on CTA was 90.9% to 100%. There was a statistically significant decrease in number of short gastric veins identified on CTA compared with surgery (P = 0.004). There was no statistically significant difference between the 2 modalities in detecting other perigastric veins including the left gastric vein, right gastric vein, right gastroepiploic vein, left gastroepiploic vein, posterior gastric vein, and gastrocolic trunk (P = 0.317, P = 0.157, P = 1, P = 1, P = 0.317, P = 1, respectively).
CONCLUSIONS: Sixty-four-slice CTA with image fusion clearly depicts most of perigastric veins and their relationship with the stomach and perigastric arteries. It can facilitate gastrectomy.


Moyes LH, McCaffer CJ, Carter RC, et al.
Cardiopulmonary exercise testing as a predictor of complications in oesophagogastric cancer surgery.
Ann R Coll Surg Engl. 2013; 95(2):125-30 [PubMed]
INTRODUCTION: An anaerobic threshold (AT) of <11 ml/min/kg can identify patients at high risk of cardiopulmonary complications after major surgery. The aim of this study was to assess the value of cardiopulmonary exercise testing (CPET) in predicting cardiopulmonary complications in high risk patients undergoing oesophagogastric cancer resection.
METHODS: Between March 2008 and October 2010, 108 patients (83 men, 25 women) with a median age of 66 years (range: 38-84 years) underwent CPET before potentially curative resections for oesophagogastric cancers. Measured CPET variables included AT and maximum oxygen uptake at peak exercise (VO2 peak). Outcome measures were length of high dependency unit stay, length of hospital stay, unplanned intensive care unit (ICU) admission, and postoperative morbidity and mortality.
RESULTS: The mean AT and VO2 peak were 10.8 ml/min/kg (standard deviation [SD]: 2.8 ml/min/kg, range: 4.6-19.3 ml/min/kg) and 15.2 ml/min/kg (SD: 5.3 ml/min/kg, range: 5.4-33.3 ml/min/kg) respectively; 57 patients (55%) had an AT of <11 ml/min/kg and 26 (12%) had an AT of <9 ml/min/kg. Postoperative complications occurred in 57 patients (29 cardiopulmonary [28%] and 28 non-cardiopulmonary [27%]). Four patients (4%) died in hospital and 21 (20%) required an unplanned ICU admission. Cardiopulmonary complications occurred in 42% of patients with an AT of <9 ml/min/kg compared with 29% of patients with an AT of ≥9 ml/min/kg but <11 ml/min/kg and 20% of patients with an AT of ≥11 ml/min/kg (p = 0.04). There was a trend that those with an AT of <11 ml/min/kg and a low VO2 peak had a higher rate of unplanned ICU admission.
CONCLUSIONS: This study has shown a correlation between AT and the development of cardiopulmonary complications although the discriminatory ability was low.


Syrios J, Kechagias G, Agrogiannis G, et al.
DNA ploidy: a prognostic factor of response to chemotherapy and survival in metastatic gastric adenocarcinoma.
Anticancer Res. 2013; 33(3):1209-14 [PubMed]
BACKGROUND: Metastatic gastric adenocarcinoma confers a dismal prognosis. Several prognostic factors are needed to distinguish patients that will benefit from chemotherapy. In this setting, the prognostic impact of DNA ploidy is still unclear.
MATERIALS AND METHODS: The records of 61 patients with metastatic gastric adenocarcinoma were retrospectively reviewed. Response to chemotherapy and overall survival (OS) were assessed and correlated to tumour DNA ploidy index, which was calculated by cytometric image analysis.
RESULTS: The median value of DNA ploidy index was 2.3. Patients with a low index responded better to chemotherapy than those with a higher index (p<0.01). Nevertheless, when the median value was used as a cut-off, no significant correlation of DNA ploidy index with response to chemotherapy (p=0.41) or OS (p=0.09) was observed.
CONCLUSION: The prognostic role of DNA ploidy in metastatic gastric adenocarcinoma is still debatable. In this study, a low DNA ploidy index was associated with favorable prognosis; however, a suitable cut-off value is not yet available.


Preusser M, Berghoff AS, Ilhan-Mutlu A, et al.
Brain metastases of gastro-oesophageal cancer: evaluation of molecules with relevance for targeted therapies.
Anticancer Res. 2013; 33(3):1065-71 [PubMed]
BACKGROUND: Brain metastases (BM) of gastro-oesophageal cancer are exceedingly rare and only limited data exist on their pathobiology.
MATERIALS AND METHODS: We identified tissue samples of BM of gastro-oesophageal cancer and analyzed the expression of human epidermal growth factor receptor-2 (HER2), phosphorylated signal transducer and activator of transcription-3 (pSTAT3), epithelial growth factor receptor (EGFR), V600E point mutation of the v-raf murine sarcoma viral oncogene homolog-B1 (BRAF V600E), cluster of differentiation molecule-34 (CD34), hypoxia inducible factor-1α (HIF 1-α) and Ki-67 by immunohistochemical methods.
RESULTS: Our series comprised of twenty adenocarcinomas and one oesophageal squamous cell carcinoma. Three (14%), 7 (33%), 9 (43%), 18 (86%) and 0 BM specimens were scored positively for HER2, EGFR, pSTAT3, HIF1-α and BRAF V600E expression. The median Ki-67 index was 59%. The microvascular density was moderate-to-high and active intratumoral microvascular sprouting was evident in 20/21 (95%) of BMs. The HER2 and EGFR expression status were consistent between primary tumors and BM in all three assessable cases. HIF1-α and pSTAT3 expression were significantly higher in HER2-positive cases.
CONCLUSION: Therapeutic use of agents targeting HER2, pSTAT3, EGFR and angiogenesis may be feasible for selected BM of gastro-esophageal cancer. HER2 positivity does not seem to predispose to brain colonization in gastro-esophageal cancer.


Pluschnig U, Schoppmann SF, Preusser M, et al.
Modified EOX (Epirubicin, Oxaliplatin and Capecitabine) as palliative first-line chemotherapy for gastroesophageal adenocarcinoma.
Anticancer Res. 2013; 33(3):1035-9 [PubMed]
BACKGROUND: The efficacy of triple-drug combination regimens such as epirubicin, oxaliplatin and capecitabine (EOX) is superior to standard cisplatin/5-fluorouracil, but considerable toxicity needs to be taken into account in patients with upper gastrointestinal adenocarcinoma. Therefore, we aimed to establish a modified version of the EOX regimen with improved tolerability for these patients.
PATIENTS AND METHODS: Patients received palliative first-line chemotherapy with a modified EOX regimen repeated every three weeks (epirubicin 50 mg/m(2) i.v., day 1; oxaliplatin 130 mg/m(2) i.v., day 1; capecitabine at a twice-daily dose of 1000 mg/m(2) p.o. for two weeks).
RESULTS: Out of 51 patients, partial remission was observed in five (10.2%) and stable disease in 31 (60.8%). Progression-free survival was four months, and overall survival twelve months.
CONCLUSION: Modified EOX was generally well-tolerated and, therefore, further investigation within prospective clinical trials is warranted.


Yang S, Liu W, Wen J, et al.
Corticotropin releasing hormone is correlated with tumorigenesis of gastric cancer.
Cancer Invest. 2013; 31(3):167-71 [PubMed]
BACKGROUND AND AIMS: The etiology of gastric cancer is unclear; its therapeutic effect is poor; the anatomical factor and lack of specific diagnostic markers are part of the reason. Recent reports indicate corticotropin releasing hormone (CRH) is associated with the pathogenesis of cancer. This study is designed to assess the levels of CRH in gastric tissue of a group of patients with gastric cancer and gastric chronic inflammation.
METHODS: Fifty-two patients with gastric cancer (GC) and 213 patients with gastric chronic inflammation were recruited into this study. The levels of CRH in the gastric biopsies were assessed. The correlation between the levels of CRH in the gastric biopsies and the tumorigenesis was assessed.
RESULTS: High levels of (458.6 pg/mg protein) CRH were detected in the biopsies of 52 patients with gastric cancer, which were also detected in the gastric biopsies of 213 patients with chronic gastritis (less than 100 pg/mg protein). CRH was below the detectable levels in the normal gastric mucosa. Of the 213 patients with chronic gastritis, 50 patients developed into cancer 3-5 years after the first diagnosis of chronic gastric cancer.
CONCLUSIONS: CRH may be involved in the pathogenesis of gastric cancer.


Kang G, Park HY, Ahn S, et al.
Heterogeneous target protein expression in synchronous multiple gastric carcinomas.
Anal Quant Cytol Histol. 2013; 35(1):27-35 [PubMed]
OBJECTIVE: To explore the target protein expression in separate tumors in a patient with synchronous multiple gastric carcinomas (SMGCs).
STUDY DESIGN: Immunohistochemistry for HER2, EGFR, and MET were performed in 282 carcinomas from 141 patients.
RESULTS: Of 141 patients with SMGCs, 11.3%, 23.4%, and 14.9% of cases showed HER2, EGFR, and MET protein overexpression, respectively. In SMGC cases with overexpression of target proteins in > 1 tumor, intertumoral heterogeneity was 81.3% (13/16) for HER2, 78.8% (26/33) for EGFR, and 90.5% (19/21) for MET protein. The concordance rate of HER2, EGFR, and MET expression between 2 carcinomas from the same patient was 90.8%, 81.6%, and 86.5%, respectively, with a kappa value below 0.3, indicating slight to fair agreement.
CONCLUSION: We found a considerable intertumoral heterogeneity of target protein overexpression in SMGCs. Our findings support a multicentric origin for SMGC and emphasize the need to perform immunohistochemistry for all synchronous lesions.


Cândido AC, de Lima Filho JL, Martins DB, et al.
Association of human papillomavirus genomic sequences by polymerase chain reaction in gastric carcinomas in Brazil.
Anal Quant Cytol Histol. 2013; 35(1):1-6 [PubMed]
OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) in patients with gastric cancer and compare with a control group.
STUDY DESIGN: Forty paraffin samples of gastric cancer and 40 endoscopic normal mucosa and peripheral blood controls were subjected to examination by polymerase chain reaction for the L1 gene of HPV. The extracted DNA was amplified in 2 reaction systems using 2 pairs of primers: MY09/MY11 and GP+5/GP+6. We used Milli-Q water as negative control and a mixture of 1 microL of human blood plus 0.25 microL of plasmid pBR322 (HPV-16) as positive control.
RESULTS: HPV was found in 4 patients with gastric cancer and 10 patients without cancer.
CONCLUSION: There was no statistically significant difference between the 2 samples (p = 0.077).


Xu ZQ, Broza YY, Ionsecu R, et al.
A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions.
Br J Cancer. 2013; 108(4):941-50 [PubMed] Article available free on PMC after 05/03/2014
Background:Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints.Methods:Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry.Results:Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and/or peptic ulcer, as compared with less severe gastric conditions. The concentrations both in the room air and in the breath samples were in the single p.p.b.v range, except in the case of isoprene.Conclusion:The preliminary results of this pilot study could open a new and promising avenue to diagnose GC and distinguish it from other gastric diseases. It should be noted that the applied methods are complementary and the potential marker compounds identified by gas-chromatography/mass spectrometry are not necessarily responsible for the differences in the sensor responses. Although this pilot study does not allow drawing far-reaching conclusions, the encouraging preliminary results presented here have initiated a large multicentre clinical trial to confirm the observed patterns for GC and benign gastric conditions.


Medina-Franco H, Cabrera-Mendoza F, Almaguer-Rosales S, et al.
Lymph node ratio as a predictor of survival in gastric carcinoma.
Am Surg. 2013; 79(3):284-9 [PubMed]
According to the American Joint Committee on Cancer (AJCC), the number of metastatic lymph nodes is the main prognostic factor in gastric cancer. Lymph node ratio (LNR) has been proposed as a better predictor of survival. We included patients resected for gastric cancer in a referral center in Mexico City. Number of metastatic nodes was analyzed according to AJCC 2002 and 2010. We divided LNR into four stages. Survival was calculated with the Kaplan-Meier method and curves compared with the log-rank test. P < 0.05 was significant. Two hundred patients were included. Median number of retrieved and metastatic nodes were 18 and 2.5, respectively. Median survival was 44 months. AJCC 2010 was a better predictor of survival than the 2002 version (P < 0.001). Median survival for LNR 0, 1, 2, and 3 was 117, 68, 44, and 14 months, respectively (P < 0.001). In patients with less than 15 nodes removed, AJCC was not a predictor of survival (P = 0.09) but LNR was (P = 0.04). Nodal staging in AJCC 2010 is a better predictor of survival than the 2002 edition. LNR is useful in the group of patients with suboptimal node dissection.


Miyake T, Nimura S, Hamada Y, et al.
MK-1 expression in gastric carcinoma with liver metastasis.
Jpn J Clin Oncol. 2013; 43(4):377-82 [PubMed]
OBJECTIVE: The prognosis for gastric carcinoma patients with liver metastasis is very poor. This retrospective study investigated the prognostic significance of MK-1 expression in gastric carcinoma patients with liver metastasis.
METHODS: Immunohistochemical staining using monoclonal antibody FU-MK-1 against MK-1 antigen was performed on paraffin-embedded tissues from 64 gastric carcinoma patients with liver metastasis. We attempted to determine the presence of any relationship between pathological prognostic factors and the expression of MK-1 in 64 gastric carcinoma patients with liver metastasis.
RESULTS: MK-1 expression was found in 43 (67%) of 64 tumor samples. MK-1 expression was significantly higher in the intestinal type (73%) than in the diffuse type carcinoma (33%, P = 0.049). Multivariate analysis showed that MK-1 expression and lymph node metastasis were significant factors for overall survival. The difference between overall survival rates with positive or negative MK-1 expression was statistically significant as shown by Kaplan-Meier survival analysis (P < 0.0001; log-rank). In addition, the difference between cumulative disease-free survival rates with positive or negative MK-1 expression in gastric carcinoma patients with metachronous liver metastasis was statistically significant as well, as shown by Kaplan-Meier survival analysis (P = 0.0006; log-rank).
CONCLUSIONS: The prognostic significance of MK-1 expression as a biological tumor marker was demonstrated in a series of gastric carcinoma patients with liver metastasis. MK-1 positivity may be a reliable marker for predicting and taking measures to control liver metastasis after curative gastrectomy for gastric carcinoma.


Imano M, Furukawa H, Yokokawa M, et al.
A Phase I/II trial of radiotherapy concurrent with TS-1 plus cisplatin in patients with clinically resectable type 4 or large type 3 gastric cancer: Osaka Gastrointestinal Cancer Chemotherapy Study Group OGSG1205.
Jpn J Clin Oncol. 2013; 43(4):431-5 [PubMed]
A Phase I/II trial of radiotherapy administered concurrently with TS-1 plus cisplatin has been initiated in Japanese patients with clinical resectable type 4 or large type 3 gastric cancer. The aim of this trial is to determine the recommended dose of TS-1 and cisplatin combined with radiotherapy at a fixed dose in the Phase I study, and to evaluate the efficacy and safety in the Phase II study. The primary endpoint for Phase II is the pathological complete response rate, assessed using surgically resected specimens. Secondary endpoints are the response rate, progression-free survival, overall survival, operation transitional rate, R0 resection rate, rate of treatment completion, rate of down-staging and rates of postoperative complications and adverse events. In Phase II, a total of 30 patients will be enrolled in the Osaka Gastrointestinal Cancer Chemotherapy Study Group trial over a period of 6 years.


Ruffato A, Mattioli S, Perrone O, et al.
Esophagogastric metaplasia relates to nodal metastases in adenocarcinoma of esophagus and cardia.
Ann Thorac Surg. 2013; 95(4):1147-53 [PubMed]
BACKGROUND: Immunohistochemical profiles of esophageal and cardia adenocarcinoma differ according to the presence or absence of Barrett's epithelium (BIM) and gastric intestinal metaplasia (GIM) in the fundus and antrum. Different lymphatic spreading has been demonstrated in esophageal adenocarcinoma. We investigated the correlation among the presence or absence of intestinal metaplasia in the esophagus and stomach and lymphatic metastases in patients who underwent radical surgery for esophageal and cardia adenocarcinoma.
METHODS: The mucosa surrounding the adenocarcinoma and the gastric mucosa were analyzed. The BIM+ patients underwent subtotal esophagectomy and gastric pull up, and the BIM- patients underwent esophagectomy at the azygos vein, total gastrectomy, and esophagojejunostomy. The radical thoracic (station numbers 2, 3, 4R, 7, 8, and 9) and abdominal (station numbers 15 through 20) lymphadenectomy was identical in both procedures except for the greater curvature.
RESULTS: One hundred ninety-four consecutive patients were collected in three major groups: BIM+/GIM-, 52 patients (26.8%); BIM-/GIM-, 90 patients (46.4%); BIM-/GIM+, 50 patients (25.8%). Two patients (1%) were BIM+/GIM+. A total of 6,010 lymph nodes were resected: 1,515 were recovered in BIM+, 1,587 in BIM-/GIM+, and 2,908 in BIM-/GIM- patients. The percentage of patients with pN+ stations 8 and 9 was higher in BIM+ (p=0.001), and the percentage of patients with pN+ perigastric stations was higher in BIM- (p=0.001). The BIM-/GIM- patients had a number of abdominal metastatic lymph nodes higher than did the BIM-/GIM+ patients (p=0.0001).
CONCLUSIONS: According to the presence or absence of BIM and GIM in the esophagus and cardia, adenocarcinoma correspond to three different patterns of lymphatic metastasization, which may reflect different biologic and carcinogenetic pathways.


Zhang Y, Wang M, Gu D, et al.
Association of XRCC1 gene polymorphisms with the survival and clinicopathological characteristics of gastric cancer.
DNA Cell Biol. 2013; 32(3):111-8 [PubMed]
Polymorphisms of the DNA repair gene X-ray repair cross-complementing protein 1 (XRCC1) Arg194Trp, Arg280His, and Arg399Gln have been shown to alter the DNA repair activity and to be associated with genetic susceptibility to several types of cancer. We indentified genotypes of 944 surgically resected gastric cancer (GC) patients by the SNaPshot method to investigate the association of these polymorphisms with clinical progression and outcomes of GC in a Chinese population. The XRCC1 codon 280 His carriers (Arg/His+His/His) held a significantly lower risk of distant metastasis in the dominant model (Pearson chi-square test P=0.019). A weak association of these cases with reduced risk of lymph node metastasis was also found (Pearson chi-square test P=0.051). Individuals carrying at least one Trp allele of XRCC1 codon 194 had an increased risk of death compared with those with Arg/Arg homozygotes in diffuse-type GC (adjusted hazard ratio=1.34, 95% confidence interval=1.05-1.71). Our findings demonstrated that the genetic variant Arg280His in XRCC1 may contribute to cancer progression and that XRCC1 Arg194Trp variants may act as a favorable prognostic indicator of resected GC, particularly among the diffuse-type GC. Larger studies are needed to verify our results in different populations.


Ali Z, Deng Y, Ma C
Progress of research in gastric cancer.
J Nanosci Nanotechnol. 2012; 12(11):8241-8 [PubMed]
Gastric cancer (GC) has continued to be a threat to human life. Diagnosis of GC at advanced stage is considered as a major reason for lower overall five-year survival rate in developing countries. A complex set of molecular irregularities occurs at cellular level during early stage of GC and its further progression will disturb normal cell functioning. These abnormalities include genetic and epigenetic modifications leading to differential expression of many genes in normal and affected cells. Many efforts are made to spot these molecular aberrations to understand the underlying mechanism which governs abnormal cell behavior. Current review summarizes recent works addressing GC etiology, epidemiology, pathology and therapy treatment.


Gong Y, He C, Duan Z, et al.
Association of two ERCC4 tagSNPs with susceptibility to atrophic gastritis and gastric cancer in Chinese.
Gene. 2013; 519(2):335-42 [PubMed]
Genetic polymorphisms in excision repair cross-complementing group 4 (ERCC4) may contribute to the risk of cancer development. However, there are few reports regarding to susceptibility to gastric cancer (GC) or its precursor, atrophic gastritis (AG). Thereby, we investigated the association between two tag single nucleotide polymorphisms (tagSNPs) rs6498486 and rs254942, which represents the majority of common SNPs of ERCC4 gene, and the risks of GC and AG development in a sex- and age-matched case-control designed study. We found that rs6498486 polymorphism was associated with a reduced AG risk in total population (for AC vs. AA: OR=0.69, 95%CI=0.52-0.94, P=0.016; for AC/CC vs. AA: OR=0.68, 95%CI=0.51-0.92, P=0.010) as well as in the subpopulation of youngers (age<60years) (for AC/CC vs. AA: OR=0.67, 95%CI=0.45-0.99, P=0.048). For the rs254942 polymorphism, compared with the common TT genotype, the genotypes of CT and CT/CC were only observed to reduce AG risk in the subgroups of males (for CT vs. TT: OR=0.64, 95%CI=0.45-0.90, P=0.012; for CT/CC vs. TT: OR=0.66, 95%CI=0.47-0.92, P=0.016) and youngers (for CT vs. TT: OR=0.72, 95%CI=0.53-0.97, P=0.035; for CT/CC vs. TT: OR=0.74, 95%CI=0.55-0.99, P=0.045). However, no significant statistical association of the two SNPs with GC susceptibility was observed in the total population. Only rs6498486 AC and AC/CC genotypes were found to be marginally associated with a reduced GC risk in the subgroup of males (for AC vs. AA: OR=0.69, 95%CI=0.49-0.99, P=0.043; for AC/CC vs. AA: OR=0.71, 95%CI=0.50-0.99, P=0.046). Our findings suggested that the ERCC4 rs6498486 and rs254942 may be associated with AG risk. Further validation of our results in larger populations and additional studies evaluating their molecular function are required.


Shenoy S, Cassim R
Metastatic melanoma to the gastrointestinal tract: role of surgery as palliative treatment.
W V Med J. 2013 Jan-Feb; 109(1):30-3 [PubMed]
BACKGROUND: Malignant melanoma is an uncommon metastatic tumor found in the gastrointestinal tract but most commonly involves the small bowel. Less than 5% of patients with metastases to the gastrointestinal tract are diagnosed antemortem. Clinical presentation could be an acute abdominal emergency such as a bowel obstruction, intussusception, bleeding and perforation or chronic symptoms with weight loss, abdominal pain and anemia.
METHODS: We report two unusual cases with acute gastrointestinal complications related to metastatic melanoma. Case 1 developed acute upper gastrointestinal bleeding and was diagnosed with gastric mass. Biopsy revealed metastatic melanoma. The patient died of his advanced disease. Case 2 with unknown primary melanoma presented with acute abdomen secondary to small bowel perforation. He underwent laparotomy and small bowel resection with palliative intent. The patient remains alive and free of symptoms at 4 year follow up.
CONCLUSIONS: Metastatic melanoma of the gastrointestinal tract should be suspected in any patient with history of cutaneous melanoma and new gastrointestinal symptoms. Surgical interventions for symptomatic patients with melanoma of the gastrointestinal tract significantly relieve pain and improve quality of life and may confer a survival advantage.


Tebbutt NC, Parry MM, Zannino D, et al.
Docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophagogastric cancer: the AGITG ATTAX2 trial.
Br J Cancer. 2013; 108(4):771-4 [PubMed] Article available free on PMC after 05/03/2014
Background:Cetuximab can reverse chemotherapy resistance in colorectal cancer. This study evaluated the efficacy and safety of the combination of docetaxel and cetuximab as a second-line treatment in docetaxel-refractory oesophagogastric cancer.Methods:Patients received docetaxel 30 mg m(-2) on days 1 and 8, every 3 weeks and cetuximab 400 mg m(-2) on day 1, then 250 mg m(-2) weekly. Biomarker mutation analysis was performed.Results:A total of 38 patients were enrolled. Response rates were PR 6% (95% CI 2-19%), s.d. 43% (95% CI 28-59%). Main grade 3/4 toxicities were febrile neutropenia, anorexia, nausea, diarrhoea, stomatitis, and acneiform rash. Median progression-free and overall survival were 2.1 and 5.4 months, respectively. A landmark analysis showed a trend to improved survival times with increased grade of acneiform rash. No KRAS, BRAF or PIK3CA mutations were observed.Conclusion:Cetuximab and docetaxel achieve modest responses rates, but maintain comparable survival times to other salvage regimens with low rates of toxicity.


Morgan DR, Torres J, Sexton R, et al.
Risk of recurrent Helicobacter pylori infection 1 year after initial eradication therapy in 7 Latin American communities.
JAMA. 2013; 309(6):578-86 [PubMed]
IMPORTANCE: The long-term effectiveness of Helicobacter pylori eradication programs for preventing gastric cancer will depend on recurrence risk and individual and community factors.
OBJECTIVE: To estimate risk of H. pylori recurrence and assess factors associated with successful eradication 1 year after treatment.
DESIGN, SETTING, AND PARTICIPANTS: Cohort analysis of 1463 randomized trial participants aged 21 to 65 years from 7 Latin American communities, who were treated for H. pylori and observed between September 2009 and July 2011.
INTERVENTIONS: Randomization to 1 of 3 treatment groups: 14-day lansoprazole, amoxicillin, and clarithromycin (triple therapy); 5-day lansoprazole and amoxicillin followed by 5-day lansoprazole, clarithromycin, and metronidazole (sequential); or 5-day lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant). Participants with a positive (13)C-urea breath test (UBT) 6 to 8 weeks posttreatment were offered voluntary re-treatment with 14-day bismuth-based quadruple therapy.
MEASUREMENTS: Recurrent infection after a negative posttreatment UBT and factors associated with successful eradication at 1-year follow-up.
RESULTS: Among participants with UBT-negative results who had a 1-year follow-up UBT (n=1091), 125 tested UBT positive, a recurrence risk of 11.5% (95% CI, 9.6%-13.5%). Recurrence was significantly associated with study site (P = .03), nonadherence to initial therapy (adjusted odds ratio [AOR], 2.94; 95% CI, 1.31-6.13; P = .01), and children in the household (AOR, 1.17; 95% CI, 1.01-1.35 per child; P = .03). Of the 281 with positive posttreatment UBT results, 138 completed re-treatment, of whom 93 tested UBT negative at 1 year. Among the 1340 who had a 1-year UBT, 80.4% (95% CI, 76.4%-83.9%), 79.8% (95% CI, 75.8%-83.5%), and 77.8% (95% CI, 73.6%-81.6%) had UBT-negative results in the triple, sequential, and concomitant groups, respectively (P = .61), with 79.3% overall effectiveness (95% CI, 77.1%-81.5%). In a single-treatment course analysis that ignored the effects of re-treatment, the percentage of UBT-negative results at 1 year was 72.4% (95% CI, 69.9%-74.8%) and was significantly associated with study site (P < .001), adherence to initial therapy (AOR, 0.26; 95% CI, 0.15-0.42; P < .001), male sex (AOR, 1.63; 95% CI, 1.25-2.13; P < .001), and age (AOR, 1.14; 95% CI, 1.02-1.27 per decade; P = .02). One-year effectiveness among all 1463 enrolled participants, considering all missing UBT results as positive, was 72.7% (95% CI, 70.3%-74.9%).
CONCLUSIONS AND RELEVANCE: One year after treatment for H. pylori infection, recurrence occurred in 11.5% of participants who had negative posttreatment UBT results. Recurrence determinants (ie, nonadherence and demographics) may be as important as specific antibiotic regimen in determining the long-term success of H. pylori eradication interventions. Study findings are relevant to the feasibility of programs for the primary prevention of gastric cancer in high-incidence regions of Latin America.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01061437.


Kunisaki C, Takahashi M, Ono HA, et al.
Biweekly Docetaxel and S-1 combination chemotherapy as first-line treatment for elderly patients with advanced gastric cancer.
Anticancer Res. 2013; 33(2):697-704 [PubMed]
BACKGROUND/AIM: This study assessed the toxicity and activity of biweekly docetaxel and S-1 combination therapy in elderly patients with advanced gastric cancer.
PATIENTS AND METHODS: One-hundred and thirteen patients were enrolled: 35 were 75 years old or more. The objective response rate, toxicity, progression-free survival (PFS), and overall survival (OS) were compared.
RESULTS: Dose reduction was significantly frequent in the elderly group (24/35 versus 25/78, p<0.001). The overall response rate was 54.9%. Out of these, 18 (15.9%) underwent gastrectomy (13 R0 gastrectomy). The median OS was 17.3 months and the median PFS was 8.0 months. Neutropenia was the most frequently observed hematological toxicity at grade 3 and 4 (34.5%), followed by leukopenia (24.8%). Most non-hematological toxicities were of grade 1 or 2. There were no significant differences in overall response rate, median OS, median PFS, or toxicities between the two groups.
CONCLUSION: This combination offers favourable survival benefits with controllable tolerance for therapy of AGC in the elderly.


DA Silva LC, Forones NM, Ribeiro DA, et al.
Immunoexpression of DIABLO, AIF and cytochrome C in gastric adenocarcinoma assessed by tissue Microarray.
Anticancer Res. 2013; 33(2):647-53 [PubMed]
The aim of this study was to analyze the immunoexpression of (Smac) DIABLO, AIF, cytochrome c, Ki-67 and cleaved caspase-3 in gastric cancer. A tissue microarray (TMA) paraffin block was constructed using gastric adenocarcinoma tissue and adjacent normal adjacent mucosa from 87 patients who had not previously undergone radiotherapy or chemotherapy. Immunohistochemistry was used to evaluate the protein levels. Samples were positive for (Smac) DIABLO in 37 (45.6%) and 37 (46.8%), for AIF in 31 (36.9%) and 36 (45.6%), for cytochrome c in 60 (68.9%) and 44 (54.4%), for Ki-67 in 63 (72.4%) and 52 (61.9%) and for cleaved caspase-3 in 21 (24.1%) and 3 (3.4%) cases of tumor and adjacent normal tissues, respectively. Our results suggest that increased expression of Ki-67 and cleaved caspase-3 could contribute to carcinogenesis. The expression of these proteins indicates an attempt of cells to maintain tissue homeostasis.


Yoshida S, Matsumoto K, Arao T, et al.
Gene amplification of ribosomal protein S6 kinase-1 and -2 in gastric cancer.
Anticancer Res. 2013; 33(2):469-75 [PubMed]
BACKGROUND: The gene amplification of ribosomal protein S6 kinase 1 and 2 (S6K1 and S6K2) and its clinical relevance in gastric cancer remain unclear.
MATERIALS AND METHODS: A comparative genomic hybridization analysis and DNA copy number assay were performed for nine cancer cell lines. The gene amplification of S6K1 and S6K2 were determined using a DNA copy number assay of 213 gastric cancer tissues.
RESULTS: S6K1 and S6K2 amplifications were observed in one and three cancer cell lines, respectively. No amplification of S6K1 was detected in the gastric cancer tissues, while S6K2 amplification was observed in 4.7% of the gastric carcinoma tissues. Patients with stage IV gastric cancer whose tumors exhibited amplification had a significantly shorter overall survival.
CONCLUSION: S6K2 amplification was frequently observed in gastric cancer and was related to a poor prognosis. Our findings may provide novel insight into the dysregulation of mammalian target of rapamycin signaling by S6K2 amplification in gastric cancer.


Yamada S, Ritchim P, Charkrabandhu T, Jongraksat W
Combination 5-fluoruracil/cisplatinum versus 5-fluoruracil/leucovorin adjuvant chemotherapy efficacy for R0 gastric resection in locally invasive gastric cancer.
J Med Assoc Thai. 2012; 95(12):1517-23 [PubMed]
BACKGROUND: The efficacy of adjuvant chemotherapy for advance resectable gastric cancer is controversial. Recently, less than 20% of the patients that received surgery can survive locally advance gastric cancer for 5 years. The purpose of the present study was to compare the therapeutic efficacy of the combination 5-fluoruracil (5-FU) with cisplatinum based and single 5-FU based regimen for the treatment of gastric cancer after post-operative gastric resection.
MATERIAL AND METHOD: Patients were recruited if they underwent curative RO gastric resection surgery with standard Dl or D2 lymph node dissection. Between 2002 and 2007, we conducted a cohort study, and collected prospective data of 88 patients with advanced gastric cancer They were analyzed for median survival time and rate, recurrence rate, and chemotherapy toxicity prevalence. The median survival time was the primary study endpoint. The median survival time was compared between groups by a log-rank test.
RESULTS: In the present study, combined 5-FU based regimen did not show a significantly superior survival time to single 5-FU regimen, both poor stage groups had better median survival in both combined 5-FU and single 5-FU regimen when compared to surgery. There was more than 50 months median survival in the first group, and 52 months in the latter However, in cisplatinum with 5-FU group, there are only a small number of signet ring cells. In addition, those have poorer clinical profile before treatment (p = 0.003). No difference on mortality rate related to toxicity.
CONCLUSION: Both regimens are useful regimens with efficient benefit for gastric cancer patients as well as a cheaper regimen than other new combination drug regimens. However second line drug or other combined second generation based chemotherapy regimen that has similar action to cisplatinum such as oxaliplatin may be safer for toxicity, and may get better out outcome. 5-FU regimen is still the reference group in future clinical trial for advanced gastric cancer treatment. The value of any new adjuvant treatment approach could be proven by a randomized study comparing it with cisplatinum based regimen plus 5-FU or single 5-FU regimen.


Rotkrua P, Shimada S, Mogushi K, et al.
Circulating microRNAs as biomarkers for early detection of diffuse-type gastric cancer using a mouse model.
Br J Cancer. 2013; 108(4):932-40 [PubMed] Article available free on PMC after 05/03/2014
BACKGROUND: Diffuse-type gastric cancer (DGC) exhibits rapid disease progression and a poor prognosis. There are no effective serum biomarkers for early detection of DGC. We have established an E-cadherin/p53 double conditional knockout (DCKO) mouse line that recapitulates human DGC morphologically and molecularly. In this study we tried to identify circulating microRNAs (miRNAs) as non-invasive biomarkers for DGC diagnosis using DCKO mice.
METHODS: We performed miRNA microarray and quantitative reverse transcription-PCR analyses of tissue and serum samples from DCKO mice with DGC and age-matched littermate controls.
RESULTS: Comparative analyses showed that mouse and human primary gastric cancers have similar miRNA expression patterns. Next, we selected some candidate miRNAs highly expressed in sera and cancer tissues of DCKO mice for further evaluation. TaqMan quantitative RT-PCR analyses indicated that four of them, miR-103, miR-107, miR-194 and miR-210, were significantly upregulated in sera of both early and advanced-stage DGC-bearing mice compared with in corresponding controls. Receiver-operating characteristic curve analyses demonstrated that these four miRNAs can discriminate DGC-positive cases from normal ones with high sensitivity and specificity.
CONCLUSION: These observations suggest that this mouse model of DGC is useful for identifying serum biomarkers, and we found circulating miRNAs that can accurately detect DGC at an early stage.


Plummer M
Helicobacter pylori and colonic neoplasms.
Am J Gastroenterol. 2013; 108(2):216-7 [PubMed]
A large cross-sectional survey suggests an association between H. pylori gastritis and colonic neoplasms, but the results should be interpreted with caution.


Xu W, Chen GS, Shao Y, et al.
Gastrin acting on the cholecystokinin2 receptor induces cyclooxygenase-2 expression through JAK2/STAT3/PI3K/Akt pathway in human gastric cancer cells.
Cancer Lett. 2013; 332(1):11-8 [PubMed]
Gastrin, cholecystokinin2 receptor (CCK2R), and cyclooxygenase-2 (COX-2) have been implicated in the carcinogenesis and progression of gastric cancer. Our study demonstrated that antagonist or siRNA against CCK2R blocked amidated gastrin (G17)-induced activation of STAT3 and Akt in gastric cancer cell lines. G17-increased COX-2 expression and cell proliferation were effectively blocked by CCK2R antagonist and inhibitors of JAK2 and PI3K. In addition, knockdown of STAT3 expression significantly attenuated G17-induced PI3K/Akt activation, COX-2 expression, and cell proliferation. These results suggest that CCK2R-mediated COX-2 up-regulation via JAK2/STAT3/PI3K/Akt pathway is involved in the proliferative effect of G17 on human gastric cancer cells.


Zhang L, Liu X, Jin H, et al.
miR-206 inhibits gastric cancer proliferation in part by repressing cyclinD2.
Cancer Lett. 2013; 332(1):94-101 [PubMed]
In this study, we detected miR-206 expression in gastric cancer (GC) and further investigated its effects on GC cell growth in vitro and in vivo. miR-206 expression was found to be significantly decreased in 30 GC samples and GC cell lines by real time-PCR. Restoration of miR-206 reduced cell growth and colony forming ability in GC cells with G0/G1 cell cycle arrest. Further studies demonstrated that miR-206 could suppress GC cells proliferation at least partially through targeting the cyclinD2 (CCND2). Therefore, we provided evidence that miR-206 was a potential tumor suppressor and may be used as a therapeutic target for gastric cancer.


Hong SW, Jung KH, Park BH, et al.
KRC-408, a novel c-Met inhibitor, suppresses cell proliferation and angiogenesis of gastric cancer.
Cancer Lett. 2013; 332(1):74-82 [PubMed]
Among many cancer therapeutic targets, c-Met receptor tyrosine kinase has recently given particular attention. This kinase and its ligand, hepatocyte growth factor (HGF), play a central role in cell proliferation and the survival of several human cancers. Thus, we developed KRC-408 as a novel c-Met inhibitor and investigated its anti-cancer effects on human gastric cancer. KRC-408 inhibited the phosphorylation of c-Met and its constitutive downstream effectors such as phosphatidylinositol 3-kinase (PI3K), Akt, Mek, and Erk. This compound was found to exert anti-cancer effects stronger than those of 5-fluorouracil (5-FU) on gastric cancer cells, especially cell lines that overexpressed c-Met. Interestingly, cytotoxicity of KRC-408 was lower than that of 5-FU in normal gastric cells. Apoptosis induced by KRC-408 was accompanied by increased levels of cleaved caspase-3 and PARP as well as DNA condensation and fragmentation. Flow cytometry analysis showed an accumulation of gastric cancer cells in the G2/M phase with concomitant loss of cells in the S phase following treatment with this drug. In the angiogenesis studies, KRC-408 inhibited tube formation and migration of human umbilical vein endothelial cells (HUVECs), and suppressed microvessel sprouting from rat aortic rings ex vivo along with blood vessel formation in a Matrigel plug assay in mice. Results of an in vivo mouse xenograft experiment showed that the administration of KRC-408 significantly delayed tumor growth in a dose-dependent manner, and suppressed Akt and Erk phosphorylation as well CD34 expression in tumor tissues. These findings indicate that KCR-408 may exert anti-tumor effects by directly affecting tumor cell growth or survival via the c-Met receptor tyrosine kinase pathway. We therefore suggest that KRC-408 is a novel therapeutic candidate effective against gastric cancers that overexpress c-Met.


Hoshyar R, Bathaie SZ, Sadeghizadeh M
Crocin triggers the apoptosis through increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma, AGS, cells.
DNA Cell Biol. 2013; 32(2):50-7 [PubMed]
We previously showed the anticancer property of crocin, a carotenoid isolated and purified from saffron against chemical-induced gastric and breast cancer in rats. In this study, the mechanism of crocin action was investigated in the gastric adenocarcinoma (AGS) cells in comparison with human normal fibroblast skin cells (HFSF-PI3). Crocin revealed a dose- and time-dependent cytotoxic effect against an AGS cell line, as determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Crocin-induced apoptosis was evidenced by flow cytometry and measuring caspase activity. The increased sub-G1 population and activated caspases in the treated AGS cells confirmed its anticancer effect. Expression of both Bax and Bcl-2 was determined using a semiquantitative reverse transcriptase-polymerase chain reaction and Western blot in these cells before and after treatment with crocin. Apoptosis was significantly stimulated as indicated by increasing the Bax/Bcl-2 ratio after crocin treatment. All of the above-mentioned parameters remained normal in HFSF-PI3 treated with crocin. These data are providing insight into the molecular mechanisms underlying the crocin-induced apoptosis in the AGS cells, rendering it as the potential anticancer agent.


This page last updated: 22nd May 2013
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