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
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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).

Deshpande G, Samarasam I, Chandran BS, et al.
Extended multiorgan resection in locally advanced gastric cancer: a single centre experience from south India.
Trop Gastroenterol. 2013 Oct-Dec; 34(4):259-63 [PubMed] Related Publications
BACKGROUND: The prognostic and survival benefit of extended multiorgan resection for locally advanced gastric adenocarcinoma remains controversial. The morbidity associated with additional organ resection has been found to be higher when compared to patients undergoing gastrectomy alone. The aim of our study was to evaluate the morbidity, mortality and survival benefit associated with extended multiorgan resection for locally advanced gastric adenocarcinoma.
METHODS: From January 2004 to December 2011, 721 patients underwent resectional surgery for gastric adenocarcinoma at the Christian Medical College, Vellore, India. Out of this group, 36 patients underwent primary resection and had one or more organs resected in addition to the stomach. A retrospective analysis of the case records of all these patients was performed. The Kaplan-Meier survival probability was estimated. Cox regression analysis was used to evaluate the clinico-pathological variables affecting the survival of these patients.
RESULTS: The perioperative morbidity and mortality rates were 25% and 5.5% respectively. The most common organs resected were colon and spleen. The incidence of pathologically confirmed T4b cancers was only 50%. The median survival of these patients was 28 months. The survival was influenced by a R0 or curative resection. However, it was not statistically significant.
CONCLUSION: Extended multiorganresection in locally advanced gastric cancer can be performed with acceptable morbidity and mortality. In our study, overstaging was found in 50% of the patients and hence, when the real nature of invasion is unclear, the surgeon may proceed with en bloc resection of the stomach with the involved adjacent organs. As long as an R0 resection can be achieved, extended multiorgan resection can be performed for carcinoma stomach.

Kim J, Jang SG, Kwon SY, et al.
MicroRNA signature for HER2-positive breast and gastric cancer.
Anticancer Res. 2014; 34(7):3807-10 [PubMed] Related Publications
BACKGROUND/AIM: The molecular mechanism for aggressive clinical behaviour related to v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) amplification is not fully-understood. In particular, little is known about microRNAs in the human epidermal growth factor receptor 2 (HER2) signaling network.
PATIENTS AND METHODS: Using microRNA microarray, the microRNA profiles of 16 HER2-positive breast carcinomas were compared with those of five luminal-type breast carcinomas. Additionally, two frozen, ERBB2-amplified gastric carcinomas were compared with their adjacent normal tissue samples. MicroRNAs that were differentially expressed according to the HER2 status in breast and gastric carcinomas were identified as the HER2 microRNA signature.
RESULTS: MiR-337 and miR-302f were commonly overexpressed in HER2-postive breast and gastric cancer. MiR-139 and miR-129 were commonly underexpressed in HER2-positive breast and gastric cancer. A concordant pattern of microRNA expression was noted between discovery sets and the majority of candidate microRNAs (two out of three) in three validation sets.
CONCLUSION: Our study identified novel microRNAs that were differentially expressed according to the HER2 status across different tumor types.

Related: Breast Cancer Signal Transduction

Kuo HY, Yeh KH
Molecular-targeted therapy for chemotherapy-refractory gastric cancer: a case report and literature review.
Anticancer Res. 2014; 34(7):3695-9 [PubMed] Related Publications
The prognosis of advanced gastric cancer (AGC) remains poor despite therapeutic advances in recent decades. Several recent positive phase III trials established the efficacy of second-line chemotherapy for metastatic gastric cancer in prolonging overall survival. However, malnutrition and poor performance of AGC in late stages usually preclude such patients from intensive treatment. Many targeted-therapies failed to show a significant survival benefit in AGC, but have regained attention after the positive result of ramucirumab was announced last year. Among all targeted agents, only trastuzumab, a monoclonal antibody against Human epidermal growth factor receptor-2 (HER2) protein, has been proven as having survival benefit by addition to first-line chemotherapy. Herein we reported a patient who benefited from adding trastuzumab to the same second-line combination chemotherapy (paclitaxel, 5-fluorouracil, and leucovorin) upon progression of bulky liver metastases. At least five months of progression-free survival were achieved without any additional toxicity. We also reviewed literature of molecularly-targeted therapy for chemotherapy-refractory gastric cancer, including several large phase III trials (REGARD, GRANITE-1, EXPAND, and REAL-3) published in 2013-2014.

Related: Trastuzumab (Herceptin)

Gonzalez-Hormazabal P, Musleh M, Bustamante M, et al.
Role of cytokine gene polymorphisms in gastric cancer risk in Chile.
Anticancer Res. 2014; 34(7):3523-30 [PubMed] Related Publications
AIM: To assess the role of pro- and anti-inflammatory polymorphisms in gastric cancer susceptibility.
PATIENTS AND METHODS: We genotyped 12 polymorphisms in eight cytokine genes (Interleukin-1β -IL1B-, IL8, IL17A, IL17F, IL32, tumor necrosis factor-α -TNF-, IL1RN, IL10) in a case-control study of 147 patients with gastric cancer and 172 controls.
RESULTS: Single polymorphism analysis revealed an association between the IL10 -592C>A single nucleotide polymorphism and cases with moderately- or well-differentiated tumors [AA vs. GG, odds ratio (OR)=3.01; 95% confidence interval (CI)=1.08-8.50]. We further analyzed gene-gene interactions using a combined attribute network implemented in multifactor dimensionality reduction software. The analysis revealed an interaction between IL8 -251A>T and IL32 rs28372698 SNPs among cases with moderately- or well-differentiated tumors. Homozygosity for both IL8 -251T and IL32 T alleles increases the odds for developing gastric cancer up to 2.63-fold (OR=2.63; 95% CI=1.15-6.03). This association was higher compared to the homozygosity for the IL8-251 T allele alone (OR=1.11; 95% CI=0.51-2.43) or the IL32 T allele alone (OR=1.21; 95% CI=0.54-2.72).
CONCLUSION: These findings suggest that IL10 -592C>A increases the odds for developing gastric cancer. An interaction between IL8 -251A>T and IL32 rs28372698 SNPs is also proposed.

Related: Cytokines TNF

Taban O, Cimpean AM, Raica M, Olariu S
PROX1 expression in gastric cancer: from hypothesis to evidence.
Anticancer Res. 2014; 34(7):3439-46 [PubMed] Related Publications
BACKGROUND: PROX1 is involved in cancer development and progression as both a tumor suppressor and oncogene. Immunohistochemical (IHC) PROX1 nuclear expression is a widely accepted pattern. Scattered data reported PROX1 IHC cytoplasmic expression in different tumors, including gastric cancer but it is not clear if this holds true.
MATERIALS AND METHODS: Evaluation of the cytoplasmic expression of PROX1 in normal gastric mucosa and gastric cancer was performed by IHC followed by RNAscope, an in situ hybridization-based method for detecting PROX1 mRNA amplification on paraffin-embedded samples and to evaluate its clinical impact.
RESULTS: Twenty five out of 48 cases of gastric cancer showed PROX1 nuclear and cytoplasmic immunohistochemical expression. Twelve out of these 20 cases positive for PROX1 on IHC (54.5%) had PROX1 mRNA gene amplification. The overlapping of PROX1 cytoplasmic expression assessed by immunohistochemistry and cytoplasmic RNAscope amplification was statistically significant (p=0.031). PROX1 mRNA gene amplification correlated with tumor grade (p=0.05) and regional lymph node metastasis as well (p=0.033). No significant correlation was obtained between PROX1 and histopathology, tumor size or distal metastasis.
CONCLUSION: A significant correlation was found between IHC and RNAscope PROX1 expression in the cytoplasm of normal and gastric cancer cells. This strongly supports its validation as a true expression on immunohistochemistry. A strong correlation between PROX1 mRNA amplification and regional lymph node metastasis supports its implications in cancer spreading and metastasis and sustains its utility, not only as a lymphatic marker, but also as a potential tumor marker in various tumor types, including gastric cancer.

Kawamura M, Tanaka K, Toiyama Y, et al.
Clinical significance of tartrate-resistant acid phosphatase type-5 expression in human gastric cancer.
Anticancer Res. 2014; 34(7):3425-9 [PubMed] Related Publications
AIM: The present study investigated the clinical significance of tartrate-resistant acid phosphatase type-5 (ACP5) expression in gastric cancer.
MATERIALS AND METHODS: In 150 specimens of gastric cancer and adjacent normal mucosa, expression of ACP5 protein and mRNA and was determined by immunohistochemical staining and quantitative real-time polymerase chain reaction, respectively.
RESULTS: Expression of ACP5 mRNA was significantly higher in cancer tissues than in adjacent normal mucosa. Elevated ACP5 mRNA was associated with lymph node metastasis and peritoneal dissemination. Logistic regression analysis revealed that elevated ACP5 expression was an independent risk factor for peritoneal dissemination and was associated with shorter survival. Immunohistochemical staining of primary carcinomas showed ACP5 to be expressed mainly in the cytoplasm.
CONCLUSION: ACP5 is predictive of peritoneal dissemination in patients with gastric cancer, and might play a crucial role in the establishment of peritoneal dissemination.

Berlth F, Mönig SP, Schlösser HA, et al.
Validation of 2-mm tissue microarray technology in gastric cancer. Agreement of 2-mm TMAs and full sections for Glut-1 and Hif-1 alpha.
Anticancer Res. 2014; 34(7):3313-20 [PubMed] Related Publications
BACKGROUND/AIM: Tissue Microarray (TMA) is a widely used method to perform high-throughput immunohistochemical analyses on different tissues by arraying small sample cores from paraffin-fixed tissues into a single paraffin block. TMA-technology has been validated on numerous cancer tissues and also for gastric cancer studies, although it has not been validated for this tumor tissue so far. The objective of this study was to assess, whether the 2-mm TMA-technology is able to provide representative samples of gastric cancer tissue.
MATERIALS AND METHODS: TMA paraffin blocks were constructed by means of 220 formalin-fixed and paraffin-embedded gastric cancer samples with a sample diameter of 2 mm. The agreement of immunohistochemical stainings of Glut-1 and Hif-1 alpha in TMA sections and the original full sections was calculated using kappa statistics and direct adjustment.
RESULTS: The congruence was substantial for Glut-1 (kappa 0.64) and Hif-1 alpha (kappa 0.70), but with an agreement of only 71% and 52% within the marker-positive cases of the full-section slides.
CONCLUSION: Due to tumor heterogeneity primarily, the TMA technology with a 2-mm sample core shows relevant limitations in gastric cancer tissue. Although being helpful for tissue screening purposes, the 2-mm TMA technology cannot be recommended as a method equal to full-section investigations in gastric cancer.

Related: SLC2A1 HIF1A

Sparks D, Bhalla A, Dodge J, Saldinger P
Isolated gastric amyloidoma in the setting of marginal zone MALT lymphoma: case report and review of the literature.
Conn Med. 2014; 78(5):277-80 [PubMed] Related Publications
A 52-year-old female presented with hematochezia. A computed topography (CT) scan revealed diffuse proximal gastric thickening with enlarged perigastric lymph nodes. The esophagogastroduodenoscopy (EGD) revealed a diffusely thickened gastric wall with hemorrhagic, friable mucosa, and multiple areas of ulceration. The biopsies showed diffuse amyloid deposition along with transmural proliferation of small- to medium-sized lymphocytes and plasma cells. The gastric mucosa showed lymphoepithelial lesions and chronic inactive gastritis. Immunohistochemical staining of the neoplastic lymphocytes revealed expression of CD20, bcl-2, bcl-10, Ki-67 proliferative index of 5%, and lambda light chain restriction. There was no expression of CD5, CD43, CD10, CD3, cyclin D1, and bcl-6. Immunophenotyping by flow cytometry revealed an abnormal B lymphocyte population with expression of CD45, CD19, CD20, and FMC7. The histomorphological, immunohistochemical and flow cytometric features were consistent with primary gastric amyloidosis associated with extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma).

Related: MALT Lymphoma

Potecă T, Potecă A, Sajin M, Comănescu M
Biological prognostic parameters in gastric carcinomas.
Chirurgia (Bucur). 2014 May-Jun; 109(3):347-54 [PubMed] Related Publications
Gastric cancer is the second leading cause of cancer mortality worldwide. (1) Gastric carcinogenesis involves a variety of factors including diet, habitual factors as well as environmental factors. (2,3) This study aimed to correlate clinicopathological parameters of the cases studied and PCNA and p53 expression using immunohistochemistry. The study group included a total of 32 patients that underwent gastrectomy for gastric cancer.The study parameters were represented by epidemiological aspects (age, sex), clinical characteristics (signs and symptoms),histopathological findings (pTNM staging and degree of differentiation, histological classification, lymph nodes status and presence of vascular invasion) and survival, and immunohistochemical analysis (p53 and PCNA expression) of the study group. Histopathological study showed that most of the cases(26 cases) were of the intestinal type and 6 cases of the diffuse type. Immunohistochemical analysis of p53 protein expression showed an average of 20.75% positive cells, while PCNA expression showed an average of 47.3%. In terms of survival there were 6 cases of death at intervals ranged from 2-189 days,5 cases had subsequent presentations over 12 months, while 8 patients were lost to follow-up. At the time of surgery, 6 patients had distant metastases, while 6 more developed them in a period of 2-12 months after surgery. Identification of biomolecules that highlight potentially aggressive tumors may help modulate the therapeutic approach after surgical resection.

Related: TP53

Esmadi M, Ahmad DS, Hammad HT
Endoscopic surveillance for gastric ulcers.
South Med J. 2014; 107(5):289-91 [PubMed] Related Publications
OBJECTIVE: Gastric ulcers (GUs) can be caused by a malignancy, and endoscopists are challenged with the question of how to rule out underlying malignancy. Although routine endoscopic surveillance is not advised, it is still overused. The purpose of this study was to explore the practice in our tertiary referral center during the last 3 years.
METHODS: We retrospectively reviewed all inpatient and outpatient esophagogastroduodenoscopies (EGDs) that were performed between November 2009 and November 2012 for GUs. Patients with GUs who normally would not undergo biopsy, such as patients who present with bleeding or had stigmata of high-risk bleeding, were excluded.
RESULTS: A total of 165 patients were diagnosed between November 2009 and November 2012 as having GUs on EGD. Fifty-two patients were excluded because they presented with bleeding or had GUs that had stigmata of high-risk bleeding. We reviewed the charts of 113 patients and endoscopic surveillance was recommended for 96 (85%). Of those 96 patients, 72 (64%) underwent repeat EGD. In those 72 patients, GU was still present in 9 patients and was completely healed or healing in 63 patients. Only 25 (22%) GUs were biopsied at initial EGD, 23 of which were benign and 2 were adenocarcinomas. No additional malignancy was found on surveillance EGD.
CONCLUSIONS: EGD surveillance for GUs is a common practice, although the guidelines discourage such a practice. Our rate of endoscopic surveillance was significantly higher than reported previously (64% vs 25%). In our experience, such a high rate of surveillance did not reveal any additional gastric malignancy. Alternatively, the rate of biopsy of GUs at initial EGD is low (22%), which also reflects endoscopists' preference for endoscopic surveillance.

Related: USA

Khalil Q, Gopalswamy N, Agrawal S
Missed esophageal and gastric cancers after esophagogastroduodenoscopy in a midwestern military veteran population.
South Med J. 2014; 107(4):225-8 [PubMed] Related Publications
OBJECTIVES: Esophagogastroduodenoscopy (EGD) with biopsy has become the standard procedure for diagnosing esophageal and gastric cancers (EGC) and is considered to have high sensitivity and specificity. To date, few studies have attempted to examine the rates of missed EGC after EGD and no study addresses the rate of missed EGC in a military veteran patient population. This led to us examine missed EGCs at our VA Medical Center across a 10-year period.
METHODS: An electronic database was used to identify patients who were diagnosed between 2000 and 2010 as having EGC. Missed cancers were defined as cancers diagnosed within 1 year of EGD, possible missed cancers as those diagnosed 1 to 3 years after EGD, and latent cancers as those diagnosed between 3 and 5 years after EGD.
RESULTS: A total of 94 patients fulfilled the study criteria: 69 had esophageal cancer and 25 had gastric cancer diagnosed at our institution during the study period. Of the included cases, one patient had a missed cancer (1.06%) and four patients had possible missed cancers (4.26%); no patients had latent cancer.
CONCLUSIONS: The true incidence of missed EGC in military veteran patients is not known. It is difficult to compare our findings to those of other studies because of the heterogeneity of studies. Our study echoes the findings of the others: EGD remains an important and effective tool in diagnosing EGC. At the same time, it also points out an important limitation, that EGC can be missed on EGD. Our findings also emphasize the importance of obtaining biopsies of any abnormality and timely clinical follow-up and by repeat EGD as needed.

Related: Cancer of the Esophagus Esophageal Cancer

Sekikawa A, Fukui H, Maruo T, et al.
Diabetes mellitus increases the risk of early gastric cancer development.
Eur J Cancer. 2014; 50(12):2065-71 [PubMed] Related Publications
BACKGROUND: The significance of diabetes mellitus (DM) in gastric carcinogenesis still remains unclear. We investigated whether DM would be a risk factor for the development of early gastric cancer.
METHODS: Factors related to the presence of gastric cancer were examined in patients undergoing medical health checkups. We then investigated whether DM was related to the development of early gastric cancer during an endoscopic follow-up study.
RESULTS: Gastric cancer was detected in 14 (1.0%) of 1463 patients at the first endoscopic examination and was significantly associated with the severity of gastric atrophy and the presence of DM. During the follow-up period (range 36-108 months; mean 70.0 months), early gastric cancer was newly detected in 26 (1.8%) of the 1449 patients in whom gastric cancer had not been detected at the first examination. Gastric cancer was detected in 17 (1.3%) of 1301 patients without DM, and in 9 (6.1%) of 148 patients with DM (P < 0.0001). Multivariate analyses demonstrated that open-type gastric atrophy and DM were independently related to the development of early gastric cancer (P < 0.0001 and P = 0.020, respectively). Gastric cancer was identified in 14 (5.1%) of 274 patients who had open-type atrophic gastritis without DM, whereas it was identified in 8 (16.0%) of 50 patients who had both open-type atrophic gastritis and DM (P = 0.0042).
CONCLUSION: DM increases the risk of early gastric cancer development.

Deng J, Zhang R, Pan Y, et al.
Comparison of the staging of regional lymph nodes using the sixth and seventh editions of the tumor-node-metastasis (TNM) classification system for the evaluation of overall survival in gastric cancer patients: findings of a case-control analysis involving a single institution in China.
Surgery. 2014; 156(1):64-74 [PubMed] Related Publications
BACKGROUND: It has recently been reported that the sixth edition of the tumor-node-metastasis (TNM) classification system for gastric cancer involving the staging of regional lymph nodes (N) has inappropriate cut-offs with regard to counts of metastatic lymph nodes. It remains controversial, however, as to whether the seventh edition of this classification system is completely accurate in staging N for the prediction of the prognosis of gastric cancer. Our aim was to determine which of these two editions of the TNM classification system was superior with regard to the prediction of the prognosis of Chinese patients with gastric cancer.
METHODS: We analyzed relevant clinicopathological data statistically from 1,563 patients with gastric cancer who had undergone curative resection to evaluate the sixth and seventh editions of the TNM classification system for N staging with regard to the prediction of overall survival (OS).
RESULTS: Our survival analyses demonstrated that N staging via use of both the sixth and seventh editions of the TNM classification system was correlated with OS. Furthermore, case-control analysis indicated that the seventh edition was significantly superior to the sixth edition in predicting the OS of patients, regardless of the extent of lymphadenectomy (D1 or D2) and the number of dissected lymph nodes (<16 or ≥16). By taking into consideration both the extent of lymphadenectomy and the number of dissected lymph nodes simultaneously, we determined that the seventh edition of the TNM classification system was superior to the sixth edition regarding the evaluation of the OS in the various subgroups of gastric cancer patients.
CONCLUSION: The seventh edition proved more reliable and accurate than the sixth edition of the TNM classification system in categorizing the number of metastatic lymph nodes for the purpose of predicting the OS of patients with gastric cancer after curative resection.

Li WQ, Ma JL, Zhang L, et al.
Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups.
J Natl Cancer Inst. 2014; 106(7) [PubMed] Article available free on PMC after 01/07/2015 Related Publications
Among 2258 Helicobacter pylori-seropositive subjects randomly assigned to receive one-time H. pylori treatment with amoxicillin-omeprazole or its placebo, we evaluated the 15-year effect of treatment on gastric cancer incidence and mortality in subgroups defined by age, baseline gastric histopathology, and post-treatment infection status. We used conditional logistic and Cox regressions for covariable adjustments in incidence and mortality analyses, respectively. Treatment was associated with a statistically significant decrease in gastric cancer incidence (odds ratio = 0.36; 95% confidence interval [CI] = 0.17 to 0.79) and mortality (hazard ratio = 0.26; 95% CI = 0.09 to 0.79) at ages 55 years and older and a statistically significant decrease in incidence among those with intestinal metaplasia or dysplasia at baseline (odds ratio = 0.56; 95% CI = 0.34 to 0.91). Treatment benefits for incidence and mortality among those with and without post-treatment infection were similar. Thus H. pylori treatment can benefit older members and those with advanced baseline histopathology, and benefits are present even with post-treatment infection, suggesting treatment can benefit an entire population, not just the young or those with mild histopathology.

Mimatsu K, Oida T, Fukino N, et al.
Glasgow prognostic score is a useful predictive factor of outcome after palliative gastrectomy for stage IV gastric cancer.
Anticancer Res. 2014; 34(6):3131-6 [PubMed] Related Publications
BACKGROUND/AIM: The Glasgow prognostic score (GPS) is a predictor of outcome for several cancer types. The present study examined the significance of modified GPS (mGPS) in the prognosis of patients undergoing palliative surgery for stage IV gastric cancer.
PATIENTS AND METHODS: A total of 42 patients with stage IV gastric cancer treated with palliative gastrectomy and gastrojejunostomy were included in the study. Univariate and multivariate analyses were performed to evaluate the relationship between clinicopathological factors and cancer-specific survival (CS).
RESULTS: Among patients who underwent palliative surgery including gastrectomy and gastrojejunostomy, univariate analysis of CS identified the following significant risk factors: surgical treatment, chemotherapy and mGPS, and multivariate analysis revealed that mGPS was independently-associated with CS. In particular, among patients who underwent palliative gastrectomy, mGPS was shown to be the strongest independent predictive factor for CS.
CONCLUSION: The mGPS was an independent predictive factor for survival in patients who underwent palliative surgery for stage IV incurable gastric cancer, especially for those who underwent palliative gastrectomy.

Donizy P, Rudno-Rudzinska J, Halon A, et al.
Intratumoral but not peritumoral lymphatic vessel density measured by D2-40 expression predicts poor outcome in gastric cancer--ROC curve analysis to find cut-off point.
Anticancer Res. 2014; 34(6):3113-8 [PubMed] Related Publications
BACKGROUND: Neolymphangiogenesis, a process of lymphatic vessel development in neoplastic tissue, may be a key event in the transmission of cancer cells into lymph nodes. The current study examined the relationship between lymphatic vessel density (LVD) measured by podoplanin (D2-40) expression, clinicopathological parameters and patient survival in gastric cancer.
MATERIALS AND METHODS: D2-40 expression was examined by immunohistochemistry in formalin-fixed paraffin-embedded tissue specimens obtained from 60 patients with gastric cancer. D2-40 immunoreactivity was analyzed in intratumoral and peritumoral compartments of tumors and correlated with tumor grade, type in Lauren's classification, lymph node status, distant metastasis, presence of ulceration, inflammatory infiltration, angio-invasion, lymphangio-invasion and patient survival using a Receiver Operating Characteristic (ROC) curve analysis to find cut-off points that enabled fair decision making in survival analysis.
RESULTS: The mean values of intratumoral and peritumoral LVD were 6.63 and 11.25, respectively. Enhanced intratumoral LVD measured by D2-40 immunoexpression was correlated with the presence of lymph node metastases (p=0.04). Our study revealed a statistically significant correlation between intratumoral LVD measured by D2-40 expression and survival of patients with gastric cancer: an intratumoral LVD higher than 4.68 is significantly correlated with unfavorable prognosis, with a probability of death of approximately 80%. No significant relationship was identified between peritumoral LVD, lymph node status and survival in patients with gastric cancer.
CONCLUSION: A high intratumoral LVD measured by D2-40 expression in specimens from primary tumors is strongly associated with lymph node metastasis and predicts worse clinical outcome. Increased intratumoral D2-40 immunoreactivity is a putative predictor of aggressive gastric cancer behavior.

Vaiopoulos AG, Kostakis ID, Gkioka E, et al.
Detection of circulating tumor cells in colorectal and gastric cancer using a multiplex PCR assay.
Anticancer Res. 2014; 34(6):3083-92 [PubMed] Related Publications
AIM: The aim of this study was the development of a multiplex-PCR assay for the detection of circulating tumor cells in patients with colorectal and gastric cancer.
PATIENTS AND METHODS: Peripheral blood samples were collected from 81 patients with colorectal cancer, 16 with gastric cancer and 38 healthy blood donors, as controls. The samples were processed for RNA extraction and cDNA synthesis and were subsequently analyzed for the expression of cytokeratin 19 (CK19), cytokeratin 20(CK20) and epidermal growth factor receptor (EGFR) with multiplex PCR.
RESULTS: Statistical analysis revealed that the combination of CK19 and CK20 could be useful in the exclusion of colorectal cancer, as well as the diagnosis and exclusion of gastric cancer. Furthermore, the expression of EGFR was correlated with the presence of systemic disease in patients with colorectal cancer.
CONCLUSION: Multiplex-PCR-based detection of circulating tumor cells could serve as a useful tool for the diagnosis, and monitoring of patients with colorectal and gastric cancer.

Related: Colorectal (Bowel) Cancer

Rubio CA, Schmidt PT
An additional case of gastric serrated adenoma.
Anticancer Res. 2014; 34(6):3007-10 [PubMed] Related Publications
Gastric serrated adenoma is an apparently rare adenoma phenotype characterized by branched villi exhibiting lateral saw-tooth indentations lined with dysplastic cells. Out of the 21 gastric serrated adenomas now in record, including the case reported here, 76% (n=16) exhibited invasive carcinoma. In contrast, only 15% of the gastric tubular/villous (that is, non-serrated) adenomas reported in the literature revealed invasive growth. Although the cause for the virulent behaviour of gastric serrated adenomas remains elusive, it would appear that not only the degree of severity of the cellular dysplasia but also the serrated ornamental configurations might play a particular role in the unusual virulence of these adenomas.

Fukuoka T, Yashiro M, Morisaki T, et al.
The role of type D prostanoid receptors and PPARγ in gastric cancer progression.
Anticancer Res. 2014; 34(6):2771-8 [PubMed] Related Publications
Prostaglandin D2 (PGD2) has been demonstrated to have antitumor effects on cancer cells. PGD2 acts through two major receptors of DP1 and DP2, as well as through the peroxisome proliferator-activated receptor γ (PPARγ) via the PGD2 metabolite, 15-deoxy-Δ12-14-PGJ2. The expression levels of DP1, DP2, and PPARγ were analyzed by immunohistochemistry on 277 primary gastric carcinomas. Either DP1- or DP2-positive cases were regarded as DP-positive. DP-Positive tumour was significantly associated with lymph mode metastasis, lymphatic invasion, and venous invasion. PPARγ positivity was not associated with any clinicopathological factors of gastric cancer. DP-Negative and PPARγ-positive cases were significantly associated with T category, lymph metastasis, and lymphatic invasion. The prognosis of DP-negative and PPARγ-positive cases was better than that of the other cases. These findings suggest that DP and PPARγ signaling influence the invasiveness of cancer cells. DP and PPARγ can be used as a potential marker for gastric cancer progression.

Related: PPARG gene

Lee T, Tanaka H, Ohira M, et al.
Clinical impact of the extent of lymph node micrometastasis in undifferentiated-type early gastric cancer.
Oncology. 2014; 86(4):244-52 [PubMed] Related Publications
OBJECTIVE: Lymph node (LN) metastasis is one of the most important prognostic factors for undifferentiated-type early gastric cancer (EGC). The aim of this study was to examine expansion of micrometastasis in regional LNs to clarify the importance of lymphadenectomy for undifferentiated-type EGC.
METHODS: Clinicopathological features of 307 patients with undifferentiated-type EGC who underwent gastrectomy with lymphadenectomy between 1997 and 2010 at the Department of Surgical Oncology, Osaka City University, were retrospectively reviewed. Micrometastasis in LNs was detected by immunohistochemistry using anticytokeratin antibody.
RESULTS: The incidence of LN metastasis was 1.8% in patients with mucosal (pT1a) tumors and 17.3% in those with submucosal (pT1b) tumors. Multivariate analysis revealed that lymphatic invasion and tumor depth were independently related to LN metastasis. Micrometastasis was found in 41 (13.3%) patients. Twenty-two patients with pN0 had micrometastasis in the perigastric region. Micrometastasis had spread to the area along the left gastric or common hepatic artery in 12 patients. Patients with an upgraded stage by micrometastasis had significantly worse disease-free survival.
CONCLUSIONS: LN micrometastasis was observed beyond the perigastric LNs and correlated with poor outcomes in patients with undifferentiated-type EGC. These data underscore the importance of adequate lymphadenectomy for patients with undifferentiated-type EGC. © 2014 S. Karger AG, Basel.

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.

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