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

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

Information for Patients and the Public (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).

Jung JH, Choi KD, Koh YW, et al.
Risk factors of lymph node metastasis in patients with gastric neuroendocrine tumor with normal serum gastrin level.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):207-13 [PubMed] Related Publications
BACKGROUND/AIMS: Locoregional gastric carcinoids with normal serum gastrin level have been recommended radical resection regardless of tumor size or depth of invasion. However, there have been some reports which showed small sporadic gastric carcinoids could be treated with local resection. The aim of this study was to elucidate risk factors of lymph node metastasis in patients with gastric carcinoids with normal serum gastrin level and determine the indications for limited resection such as endoscopic treatment.
METHODOLOGY: We performed clinicopathologic reviews of thirty gastric carcinoids with normal serum gastrin level from January 1996 to December 2010.
RESULTS: One case show distant metastasis and two cases showed lymph node metastasis at the time of diagnosis. For twenty seven cases which showed no regional lymph node or distant metastasis initially no additional lymph node or distant metastasis were diagnosed throughout the follow up period. Large tumor size (>10 mm), proper muscle infiltration, WHO classification grade 2 and lymphovascular invasion was noted risk factor of lymph node metastasis by univariate logistic regression analysis.
CONCLUSIONS: Small (≤10 mm) gastric carcinoids with normal serum gastrin level confined to submucosa can be treated with endoscopic or local resection unless lymphovascular invasion.

Kong W, Wang J, Ping X, et al.
Biomarkers for assessing mucosal barrier dysfunction induced by chemotherapy: Identifying a rapid and simple biomarker.
Clin Lab. 2015; 61(3-4):371-8 [PubMed] Related Publications
BACKGROUND: Chemotherapy-induced mucosal barrier dysfunction is of clinical interest. However, the assessment of mucosal barrier dysfunction still poses challenges. In this study, we compared several biomarkers with the dual sugar gut permeability test for assessing mucosal barrier dysfunction during chemotherapy.
METHODS: Forty-two patients with gastric or colorectal cancer underwent chemotherapy, including FAM or FOLFOX4 regimens. Patients were asked to grade and record their symptoms of gastrointestinal toxicity daily. The urinary lactulose-mannitol ratio was measured to assess the intestinal permeability. Plasma levels of citrulline, diamine oxidase (DAO), D-lactic acid, and endotoxin were also measured. Intestinal permeability was observed in the subgroup of patients with diarrhea or constipation.
RESULTS: The urinary lactulose-mannitol ratio and plasma citrulline levels increased on the third and sixth post-chemotherapy days, respectively. There were no significant differences in the plasma levels of D-lactic acid, endotoxin or DAO activity compared to their levels before chemotherapy. The urinary lactulose-mannitol ratio in diarrhea patients was significantly higher than in constipation patients.
CONCLUSIONS: These results indicate that the urinary lactulose-mannitol ratio and plasma citrulline level are appropriate biomarkers for assessing mucosal barrier dysfunction in patients receiving chemotherapy. Mucosal barrier dysfunction in diarrhea patients was greater than in constipation patients.

Related: Colorectal (Bowel) Cancer

Shen Z, Yu J, Lei S, et al.
Glycemic changes after gastrectomy in non-morbidly obese patients with gastric cancer and diabetes.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):245-50 [PubMed] Related Publications
BACKGROUND/AIMS: To evaluate the glycemic changes after gastrectomy in non-morbidly obese patients with gastric cancer (GC) and type 2 diabetes mellitus (T2DM).
METHODOLOGY: Between December 2011 and June 2014, we included 46 patients with gastric cancer and T2DM of a body mass index (BMI) < 30 kg/m2, who underwent gastrectomy in our center. The comparisons of FPGs in specific periods were performed according to age, extent of gastrectomy, reconstruction type, preoperative triglyceride (TG) level and so on.
RESULTS: The non-morbidly obese patients experienced an improvement of glycemic control. T2DM resolution happened 3 weeks after surgery. FPG decreased significantly after postoperative day 21 compared to preoperative FPG. 32 patients experienced DM improvement after postoperative day 21. The age and relatively lower preoperative TG patients, who underwent total gastrectomy (P<0.001) or duodenal bypass reconstruction (Billroth II, Roux-en-Y gastrojejunostomy, or Roux-en-Y esophagojejunostomy, P=0.009) appeared to have a better glycemic control.
CONCLUSIONS: Our finding observed through this simulation model suggested that non-morbidly obese patients may also benefit from metabolic surgery for glycemic control, associated with age, extent of gastrectomy, reconstruction type, and preoperative triglyceride level.

Lan H, Zhu N, Lan Y, et al.
Laparoscopic gastrectomy for gastric cancer in China: an overview.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):234-9 [PubMed] Related Publications
Since its introduction in China in 2000, laparoscopic gastrectomy has shown classical advantages of minimally invasive surgery over open counterpart. Like all the pioneers of the technique, Chinese gastrointestinal surgeons claim that laparoscopic gastrectomy led to faster recovery, shorter hospital stay and more rapid return to daily activities respect to open gastrectomy while offering the same functional and oncological results. There has been booming interest in laparoscopic gastrectomy since 2006 in China. The last decade has witnessed national growth in the application of laparoscopic gastrectomy and yielded a significant amount of scientific data to support its clinical merits and advantages. However, few prospective randomized controlled trials have investigated the benefits of laparoscopic gastrectomy in China. In this article, we make an overview of the current data and state of the art of laparoscopic gastrectomy for gastric cancer in China.

Qiu Z, Sun W, Zhou C, Zhang J
HER2 expression variability between primary gastric cancers and corresponding lymph node metastases.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):231-3 [PubMed] Related Publications
BACKGROUND/AIMS: The efficacy of anti-HER2 therapy is mainly dependent on HER2 overexpression in the metastatic lesions. It is essential to decipher the heterogeneity of gene profiles between primary tumor and matched metastases in gastric cancer.
METHODOLOGY: The frequency of HER2 expression in 100 gastric cancers of both primary tumors and corresponding multiple lymph node metastases were determined immunohistochemically. A modified HER2-scoring criteria by Hofmann et al recommended for gastric cancer were followed in our study, which considers basolateral, so-called "U-shape", HER2-expression as positive.
RESULTS: HER2 overexpression (2+, 3+) was seen in 33.0% of primary gastric cancers and 39.4% of the corresponding metastatic lymph nodes. For the first time, we compare HER2 expression heterogeneity among different lymph node metastases in the same patient, for the cases with 2 or more metastatic lymph nodes, HER2 expression discordance among the nodes was observed in 25.3% of the cases.
CONCLUSIONS: HER2 overexpression was seen in one-third of primary gastric cancers with lymph node metastases. As the receptor expression may lose or gain in the metastases at a probability of approximately 30%, assessment of the receptor status in metastatic lesions is encouraged.

Zu H, Wang H, Li C, et al.
Clinico-pathological features and prognostic analysis of gastric cancer patients in different age groups.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):225-30 [PubMed] Related Publications
BACKGROUND/AIMS: The prognostic value of age on patients with gastric cancer is not well defined. The aim of this retrospective study is to analyze the impact of age on survival in patients with gastric cancer.
METHODOLOGY: A total of 1800 patients with gastric carcinoma, who had undergone gastrectomy between 1997-2007 years were included. They were divided into six different age groups (21-30, 31-40, 41-50, 51- 60, 61-70 and 71-80 years). We reviewed patient's clinico-pathological characteristics and the prognosis with special reference to their ages.
RESULTS: Among the six age groups, the younger patients have more female-dominated patients and poorly differentiated carcinoma, whereas the older patients have a higher incidence of large tumors (≥5 cm) and more patients with stage T3. Moreover, there were more liver metastases in the older age groups. Univariate analysis showed that there were significant differences in 5-year survival rates among the six age groups. Multivariate analysis confirmed age, tumor size, pT stage, pN stage and curability were independent prognostic factors.
CONCLUSION: There are several distinctive properties related to age of patients with gastric cancer, the older patients have more aggressive features and poorer prognosis than the younger patients.

Nakamura M, Tahara T, Shiroeda H, et al.
The effect of short-term proton pump inhibitor plus anti-ulcer drug on the healing of endoscopic submucosal dissection-derived artificial ulcer: a randomized controlled trial.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):219-24 [PubMed] Related Publications
BACKGROUND/AIMS: Artificial ulcers remain a major complication after Endoscopic submucosal dissection (ESD). The development of more effective treatment regimen for this ulcer is required than the use of proton pump inhibitor (PPI) alone.
METHODOLOGY: Patients with ESD-derived artificial ulcers were randomly assigned to two groups: a group of patients who received rabeprazole 20 mg daily for 8 weeks (PPI group) and a group of patients who received a combination of rebamipide 300 mg daily for 8 weeks and rabeprazole 20 mg dairy for the first 4 weeks (reb+PPI group). The area reduction ratio and healing status of ulcers were evaluated endoscopically on postoperative 7, 28 and 56 days.
RESULTS: The overall ulcer area reduction ratio was higher in the reb+PPI group than in the PPI group, especially at an early stage. The ratio of progression to the H1 stage in the reb+PPI group was significantly higher than that in the PPI group, especially at an early stage.
CONCLUSIONS: Treatment with 8 weeks of rebamipide plus the first 4 weeks of PPI demonstrated a reduction ratio of artificial ulcers superior to that with 8 weeks of PPI mono-therapy. This combination treatment is, therefore, one of the candidate treatment strategies against ESD-derived artificial ulcers.

Kikuchi S, Mieno H, Moriya H, et al.
A preliminary study on pre-operative tumor volumetry measured by three-dimensional computer tomography in gastric cancer.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):214-8 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of the present study was to evaluate the clinical significance of tumor volumetry measured by three-dimensional (3-D) multidetector row computed tomography (MD-CT).
METHODOLOGY: A total of 50 patients with gastric cancer who had undergone pre-operative tumor volumetry using 3D-MD-CT followed by subsequent laparotomy (11 women, 39 men; mean age 63.9 years) were examined. Tumor volume and conventional clinicopathological factors were studied and then analyzed with respect to survival.
RESULTS: Tumor volume was distributed widely and ranged from 0.16 cm3 to 363.5 cm3 with a mean of 43.6 cm3 (<10 cm3, 21 tumors; ≥10 cm3, 29 tu- mors). Significant differences in survival were found for volume (<10.0 cm3 vs. ≥10.0 cm3; p=0.0414), and depth of invasion (T1-2 vs. T3-4; p=0.0475), but not for diameter (<50 mm vs. ≥50 mm; p=0.2142), location (proximal third vs. middle or distal third; p=0.3254), macroscopic type (localized vs. invasive; p=0.3619), or microscopic type (differentiated vs. undifferentiated; p=0.1230).
CONCLUSIONS: The present findings suggest that tumor volume measured by pre-operative 3D-MD-CT offers an alternative indicator for determining the prognosis in gastric cancer.

Hu HK, Ke NW, Li A, et al.
Clinical characteristics and prognostic factors of gastroenteropancreatic neuroendocrine tumors: a single center experience in China.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):178-83 [PubMed] Related Publications
BACKGROUND/AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a unique subgroup of tumors in the digestive system but with great clinical heterogeneity. The information on clinical characteristics and prognostic factors of Chinese patients is rather limited.
METHODOLOGY: We retrospectively analyzed the clinical features, prognostic factors of this disease in a consecutive cohort (N=294) between January 2007 and December 2012.
RESULTS: Functioning tumors accounted for 9.2%. Rectum was the most predominant GEP-NETs locations. Abdominal pain occurred in 46.5% patients which was the most common initial symptom. G1, G2 and G3 tumors accounted for 41.5%, 34.7% and 23.8%, respectively. Endoscopy provided the highest detection rate of 95.7%. Consistence between endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNAB) and surgically obtained histological Ki-67 index was 36.4%. Serum CgA test showed a 80.0% consistence with the tissue biopsy. The median follow up duration was 2.8 years (0.02-5.90 years), the median survival was 4.8 years, overall 5-year survival rate was 69.6%. We found colonic localization, tumor size larger than 20 mm, G3 tumor and metastasis were associated with worse outcome (p<0.05).
CONCLUSION: We found both consistence and differences in GEP-NETs characteristics between our study and previous reports.

Related: MKI67 Cancer of the Pancreas Pancreatic Cancer

Kasetsermwiriya W, Nagai E, Nakata K, et al.
Surgery of upper GI gastrointestinal stromal tumors: our experience, prognostic analysis.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):87-92 [PubMed] Related Publications
BACKGROUND/AIMS: To review our treatment experience of gastrointestinal stromal tumors (GISTs) of the upper gastrointestinal tract and identify the prognostic factors that influence tumor recurrence.
METHODOLOGY: Data of 46 consecutive patients with upper GI GISTs who underwent surgery from 1988 to 2011 were reviewed. The overall and disease-free survival rates and influence of clinicopathologic variables on disease-free survival rate were evaluated.
RESULTS: The median age was 64 years (range, 20-86 years). R0 resections were performed in 43 (93.5%) patients. With a median follow-up time of 33 months (1-275 months), there were 5 (10.9%) recurrences and 2 mortalities in the high-risk group. The overall survival and recurrence-free survival rates at 5 years were 92.1% and 84.6%, respectively. Male gender, tumor size of >10 cm, high numbers of mitotic figures, R1 resection, high risk according to the Joensuu criteria, and a Ki-67 index of >10% were associated with a poor prognosis.
CONCLUSIONS: Surgical resection of low- and intermediate-risk GISTs has excellent results. High counts of mitotic figures, male gender, incomplete resection, large tumor size, and a high Ki-67 index are associated with a poor prognosis.

Related: Gastrointestinal Stromal Tumors MKI67

Ren X, Zhao Z, Huang W, et al.
Analysis of the characteristics and factors influencing lymph node metastasis in thoracic esophageal carcinoma and cancer of the gastric cardia.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):73-6 [PubMed] Related Publications
BACKGROUND/AIMS: To analyze the metastatic characteristics of lymph nodes in thoracic esophageal carcinoma and cancer of the gastric cardia, and to explore the factors influencing lymph node metastasis.
METHODOLOGY: A retrospective analysis of the treatment of 37 patients who received surgical treatment for thoracic esophageal and gastric cardia cancers from January 2010 to January 2012 was carried out,
RESULTS: Lymph node metastasis in patients with thoracic esophageal carcinoma was frequently found on the superior mediastinum, hilum of the lung, and inferior extremity of the carina. Metastasis in patients with cancer of the gastric cardia occurred mainly in the abdominal cavity and peripheral gastric cardia. A single factor analysis showed that a tumor infiltrating full-thickness, > 5 cm in length, and with a low degree of cell differentiation affected lymph node metastasis (P < 0.05). The degree of differentiation, length, and infiltrating depth of the tumor were independent factors affecting lymph node metastasis (P < 0.05).
CONCLUSIONS: Lymph node metastasis in patients with cancers of the esophagus and gastric cardia exhibits special characteristics. The cleaning scope should be assessed according to the actual situation, including the degree of tumor differentiation, lesion length, and infiltration depth.

Related: Cancer of the Esophagus Esophageal Cancer

Zhang S, Lee DS, Morrissey R, et al.
Early or late antibiotic intervention prevents Helicobacter pylori-induced gastric cancer in a mouse model.
Cancer Lett. 2015; 359(2):345-51 [PubMed] Related Publications
H. pylori infection causes gastritis, peptic ulcers and gastric cancer. Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer remains unknown, especially if given after intestinal metaplasia has developed. H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking the tumor suppressor p27 do so, thus providing an experimental model of H. pylori-induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8 weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls. Mice in the eradication arms received antimicrobial therapy (omeprazole, metronidazole and clarithromycin) either "early" (at 15 weeks post infection, WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori determination, histopathology and cytokine/chemokine expression. Persistently infected mice developed premalignant lesions including high-grade dysplasia, whereas those given antibiotics did not. Histologic activity scores in the eradication groups were similar to each other, and were significantly decreased compared with controls for inflammation, epithelial defects, hyperplasia, metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received antibiotics were significantly lower than controls. There were no significant differences in expression of IFN-γ, TNF-α, IL-1β, RANTES, MCP-1, MIP-1α or MIP-1β among the three groups. Thus, H. pylori eradication given either early or late after infection significantly attenuated gastric inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient mice model of H. pylori-induced gastric cancer, irrespective of the timing of antibiotic administration. This was associated with reduced expression of IP-10 and MIG.

Alkan A, Mızrak D, Utkan G
Lower folate levels in gastric cancer: is it a cause or a result?
World J Gastroenterol. 2015; 21(13):4101-2 [PubMed] Free Access to Full Article Related Publications
Folate deficiency and its association with cancer have been studied in the literature, but its clinical impact is still unknown. Folate deficiency and its result on gastric cancer is a mysterious part of oncology, with ongoing studies hopefully clarifying its impact on gastric cancer management. Lee et al studied folate deficiency and its impact on staging and clinical results. Here we try to contribute to the field by expressing our own thoughts about the paper.

Giorlandino A, Caltabiano R, Gurrera A, Lanzafame S
Gastrointestinal stromal tumour of the stomach with osseous differentiation: a case report.
Pathologica. 2014; 106(4):345-7 [PubMed] Related Publications
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract, while osseous metaplasia of this tumour is an unexpected event. To date, no cases have been reported in the literature. Herein, we report a case of a 60-year-old man affected by a GIST with benign osseous metaplasia and mature bone formation. We also discuss the pathogenesis of intratumoural ossification and review the relevant literature. The prognostic significance of ossification in GIST remains unclear because of the limited cases reported.

Related: Gastrointestinal Stromal Tumors

Okuchukwu EH, Olayiwola OA
Epidemiology and clinicopathological characteristics of gastric cancer--the Nigerian setting in view.
Niger J Med. 2015 Jan-Mar; 24(1):71-80 [PubMed] Related Publications
BACKGROUND: Gastric cancer is the 5th most common cancer globally and the 3rd most common killer cancer, although in Nigeria it is the 9th most common cancer with a dismal prognosis.
AIM: To review the epidemiological and clinicopathological features of gastric cancer in Nigeria in the last two decades.
MATERIALS AND METHODS: Original articles and review articles published about gastric cancer in Nigeria in the last two decades were reviewed.
RESULTS: Most studies that have been done on gastric cancer in Nigeria, and which have been included in this review are hospital-based studies. With the exception of the lower prevalence of the disease and the younger peak age prevalence of gastric cancer in the Nigerian population, the epidemiological and clinicopathological features of gastric cancer are similar to those from other populations. Also, there has been an improvement in the overall survival of gastric cancer in Nigeria over the last three decades.
CONCLUSION: The prevalence of gastric cancer in the Nigerian population has remained relatively low over the decades while it continues to share similar mode of presentation with other populations, with some improvement in prognosis.

Xu Q, Liu JW, Yuan Y
Comprehensive assessment of the association between miRNA polymorphisms and gastric cancer risk.
Mutat Res Rev Mutat Res. 2015 Jan-Mar; 763:148-60 [PubMed] Related Publications
Single nucleotide polymorphisms (SNPs) in pri- or pre-microRNAs (miRNAs) were found to be associated with gastric cancer risk. The aim of this study was to systematically review with update meta-analysis for the association of miRNA SNPs with gastric cancer risk. We systematically reviewed a total of 31 SNPs in the precursor genes of 29 miRNAs associated with overall cancer risk. Meanwhile, 13 case-control studies with a total of 9044 gastric cancer cases and 11,762 controls were included in a meta-analysis of five highly studied pre-miRNA SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-499 rs3746444, miR-149 rs2292832 and miR-27a rs895819). Our results show both the homozygous miR-27a rs895819 and the miR-149 rs2292832 heterozygote genotype were associated with a decreased risk of gastric cancer when compared with wild type. In the stratified analysis, in some subgroup, heterozygous miR-146a rs2910164 was associated with a decreased risk of gastric cancer; and the variant genotype of miR-196a-2 rs11614913 was associated with an increased risk. No association was found between miR-499 rs3746444 and gastric cancer risk. In summary, miR-27a rs895819 and miR-149 rs2292832 are of potential forewarning ability for gastric cancer risk.

Related: MicroRNAs

Çalik M, Demirci E, Altun E, et al.
Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer.
Turk J Med Sci. 2015; 45(1):118-28 [PubMed] Related Publications
BACKGROUND/AIM: To assess the prognostic value of Ki-67, p27, and p53 immunoreactivity in human gastric cancer.
MATERIALS AND METHODS: A total of 84 patients with gastric cancer participated in our study. We categorized tumors as intestinal and diffuse types, with reference to Lauren's classification. Ki-67, p27, and p53 immunoreactivity were correlated with patient's age, tumor type, grade, lymph node status, extent of invasion, tumor-node-metastasis (TNM) stage, and survival.
RESULTS: Decreased expression of p27 (<20% positivity of cells) and increased p53 staining (>50% positivity of cells) were determined in 41 (48.8%) and 29 (36.9%) tumor specimens, respectively, and were connected with both the TNM stage (P = 0.007 and P = 0.039, respectively), and the extent of tumor invasion (P = 0.025 and P = 0.004, respectively). Kaplan-Meier methods showed a remarkable effect of reduced p27 expression on survival time (P = 0.003). In contrast, we observed no notable relationship between survival time and p53 or Ki-67 immunoreactivity (P = 0.372 and P = 0.401, respectively).
CONCLUSION: A decrease in p27 expression and overexpression of p53 or Ki-67 may cause advancing and metastatic illness in patients with gastric carcinoma. In addition, immunopathological identification of p27 may be helpful to define patients with gastric cancer who are at an increased risk of death.

Related: CDKN1B MKI67 TP53

Bilgiç CI, Tez M
Serum VEGF levels in gastric cancer patients: correlation with clinicopathological parameters.
Turk J Med Sci. 2015; 45(1):112-7 [PubMed] Related Publications
BACKGROUND/AIM: To evaluate the predictive role of the circulating levels of vascular endothelial growth factor (VEGF) in gastric cancer patients.
MATERIALS AND METHODS: This study is a case-control study. We measured serum VEGF levels of 30 patients aged between 34 and 83 years with gastric cancer and 30 patients without malignant pathology, operated on for benign pathologies, with ages ranging from 18 to 69.
RESULTS: Serum levels of VEGF were correlated with the tumor type classification (signet cell adenocarcinoma) and the presence of adjacent tissue invasion. There was also a positive correlation between serum VEGF and carcinoembryonic antigen levels.
CONCLUSION: In gastric cancer patients, serum VEGF levels may provide additional prognostic information for preoperative evaluation of invasion and tumor type.

Related: VEGFA

Jeong O, Kyu Park Y, Ran Jung M, Yeop Ryu S
Analysis of 30-day postdischarge morbidity and readmission after radical gastrectomy for gastric carcinoma: a single-center study of 2107 patients with prospective data.
Medicine (Baltimore). 2015; 94(11):e259 [PubMed] Related Publications
PD morbidity and readmission pose a substantial clinical and economic burden to the healthcare system. Comprehensive PD complications and readmission data are essential for developing initiatives to improve patient care. No previous studies have extensively investigated PD complications after gastric cancer surgery.We investigated the incidence, types, treatment, and risk factors of 30-day postdischarge (PD) complications after gastric cancer surgery.Between 2010 and 2013, data concerning complications and readmission within 30 days of hospital discharge were prospectively collected in 2107 patients undergoing gastric cancer surgery.In total, 1642 patients (77.9%) underwent distal gastrectomy, 418 (19.8%) total gastrectomy, and 47 (2.3%) other procedures. Postoperative morbidity and mortality were 17.4% and 0.6%, respectively, with a mean 8.8-day hospital stay. Sixty-one patients (2.9%) developed 30-day PD morbidity (58 local and 3 systemic complications), accounting for 16.6% of overall morbidity; 47 (2.2%) were readmitted; and 7 (0.3%) underwent a reoperation. The mean time to PD complications was 9.5 days after index hospital discharge. The most common complication was intra-abdominal abscess (n = 14), followed by wound, ascites, and anastomosis leakage. No mortality occurred resulting from PD complications. In the univariate and multivariate analyses, underlying comorbidity (hypertension and liver cirrhosis) and obesity were independent risk factors for developing PD complications.The early PD period is a vulnerable time for surgical patients with substantial risk of complication and readmission. Tailored discharge plans along with appropriate PD patient support are essential for improving the quality of patient care.

Cetinkunar S, Guzel H, Emre Gokce I, et al.
High levels of platelet/lymphocyte ratio are associated with metastatic gastric cancer.
J BUON. 2015 Jan-Feb; 20(1):78-83 [PubMed] Related Publications
PURPOSE: The predictive and prognostic value of cheap, easily accessible and commonly available complete blood count parameters has already been studied in a variety of cancers. In the present study, we aimed to investigate the association between pretreatment platelet/lymphocyte ratio (PLR) and metastatic gastric cancer.
METHODS: The records of 228 patients dating from January 2010 to June 2014 were retrospectively evaluated. Patients who had undergone radical (N=157) or palliative gastrectomy (N=71) for metastatic gastric cancer were included and divided into two groups according to stage (early-advanced) and metastasis (absence-presence) status, and PLR values were compared.
RESULTS: 38 (16.6%) of 228 patients had early gastric cancer (non metastatic cases). PLR values of advanced gastric cancer (not including metastatic cases) were significantly higher compared to early gastric cancer (231.6±107.45 and 160.3±71.5, respectively; p<0.001). Seventy one (31.1%) of 228 patients had distant metastasis. PLR values of metastatic gastric cancer were significantly higher than in non-metastatic gastric cancer (251.0±94.8 and 192.7±88.8, respectively; p<0.001). Logistic regression analysis showed that PLR was an independent predictive factor for tumor burden in both stage and metastasis groups (p<0.001 and p=0.003, respectively). Also, in correlation analysis, PLR showed mild correlation with stage and metastasis groups (r=0.291 and r=0.299, respectively).
CONCLUSIONS: Pretreatment PLR values were correlated with tumor burden, and most higher values were detected in metastatic disease. Our findings may be useful, especially in the decision-making for laparoscopic staging in patients who have no radiological evidence of metastatic disease.

Zhang L, Xiao A, Ruggeri J, et al.
The germline CDH1 c.48 G>C substitution contributes to cancer predisposition through generation of a pro-invasive mutation.
Mutat Res. 2014; 770:106-11 [PubMed] Related Publications
Mutation screening of CDH1 is a standard of care for patients who meet criteria for Hereditary Diffuse Gastric Cancer (HDGC). In this setting, the classification of the sequence variants found in CDH1 is a critical step for risk management of patients with HDGC. In this report, we describe a germline CDH1 c.48 G>C variant found in a 21 year old woman and her living great uncle, who were both diagnosed with gastric cancer and belong to a family with high incidence of this type of cancer. This variant occurs at the last nucleotide of exon 1 and presumably results in a Gln-to-His change at codon 16 (Q16H). We used cloning strategies to evaluate the effects on mRNA stability and found that 5/27 and 0/17 clones have the "C" mutant allele in patient and her great uncle, respectively. In vitro functional studies revealed that the germline missense mutant (Q16H) had a pro-invasive cell behavior. Both results (functional and clinical) support the conclusion that the CDH1 c.48 G>C (Q16H) variant contributes to HDGC through the generation of a pathogenic missense mutation with loss of anti-invasive function.

Related: CDH1

Zhang QY, Cheng WX, Li WM, et al.
Occurrence of low frequency PIK3CA and AKT2 mutations in gastric cancer.
Mutat Res. 2014; 769:108-12 [PubMed] Related Publications
The PI3K/AKT signal transduction pathway has distinct functional roles in tumor progression. PIK3CA was reported to harbor the hot-spot in many types of tumor. Akt, the downstream of PI3K, its family members especially AKT2 activation in human cancer has been extensively studied, but its activation by mutation was less reported. The occurrence of PIK3CA and AKT2 mutations in a variety of cancers indicates their important involvement in carcinogenesis. Therefore, we investigated their mutation frequencies in gastric cancer (GC) in China. In our study, we selected hot-spot related exons 9, 18 and 20 of PIK3CA and kinase domain exons 6-14 of AKT2 genes were screened in 10 GC cell lines, 100 advanced primary GC and matched normal tissues. Denaturing high performance liquid chromatography (DHPLC) and DNA sequencing were used to analyze the mutations in the two genes. Two point mutations in the PIK3CA gene were identified in 4 of 10 GC cell lines and in 4 of 100 GC primary tumors. Two polymorphisms in AKT2 were detected in 19 of 100 GC primary tumors. One point mutation in AKT2 was detected in 1 of 10 GC cell lines and 3 of 100 GC primary tumors but no hot spot variation was detected. Our results indicate that PIK3CA and AKT2 mutations occurred at low frequency in GC, and suggest that the PIK3CA/AKT2 pathway might engage other events during gastric carcinogenesis.

Related: AKT1 AKT2

Wang S, Lv C, Jin H, et al.
A common genetic variation in the promoter of miR-107 is associated with gastric adenocarcinoma susceptibility and survival.
Mutat Res. 2014; 769:35-41 [PubMed] Related Publications
BACKGROUND: Global miRNA expression profile has been widely used to characterize human cancers. It is well established that genetic variants in miRNAs can modulate miRNA biogenesis and disease risk.
METHODS: Genome-wide miRNA microarray was employed for assessment of miRNA expression profile of gastric adenocarcinoma (GAC). The variants of significantly dysregulated miRNA were genotyped in test (715 cases and 804 controls) and validation (940 cases and 1050 controls) subject sets.
RESULTS: MiRNA microarray revealed that 12 miRNAs including miR-107 significantly dysregulated in GAC tissues. The sequencing of the promoter of miR-107 identified 3 SNPs (rs11185777, rs78591545, and rs2296616) with minor allele frequency (MAF)>5%. Analyzing their association with GAC risk and prognosis revealed that the C allele of rs2296616 (T>C) was significantly associated with the decreased risk of GAC among the test, validation and combined sets (TC/CC vs. TT, adjusted OR=0.39, 95% CI=0.31-0.49 for the combined set). However, the C allele was related to an unfavorable prognosis of Cardia GAC (CGAC) (adjusted HR=1.49, 95% CI=1.01-2.20). In vivo evidence showed that the individuals with the rs2296616C allele had lower miR-107 expression compared with the homozygous T allele carriers.
CONCLUSION: miR-107 is dysregulated in GAC pathogenesis and the SNP rs2296616 may play a role in the process.

Related: MicroRNAs MicroRNA miR-107

Jeong HJ, Koo BS, Kang TH, et al.
Inhibitory effects of Saururus chinensis and its components on stomach cancer cells.
Phytomedicine. 2015; 22(2):256-61 [PubMed] Related Publications
Saururus chinensis (SC) Baill. (Saururaceae), a perennial herb commonly called Chinese lizard's tail or Sam-baekcho in Korea, has been used in the treatment of edema, gonorrhea, jaundice, and inflammatory diseases. Recently, several reports have been commissioned to examine the anti-cancer activities of this plant. In this study, we evaluated the inhibitory activity and mechanism of action on SC and its components against stomach cancer cells. SC extracts displayed cytotoxic effects on AGS cells in a dose-dependent manner. Moreover, SC increased the number of annexin V-positive apoptotic bodies and phosphorylated JNK and p38 in AGS cells. SC also down-regulated anti-apoptotic (Bcl-2) genes and up-regulated apoptotic (Bax) genes in AGS cells. We further confirmed that caspase activation plays an important role in SC-induced apoptosis in AGS cells. Furthermore, we examined erythro-Austrobailignan-6 and meso-dihydroguaiaretic acid, major active constituents of SC, which induced apoptosis in both the AGS and NCI-N87 stomach cancer cell lines. Taken together, our data provide the evidence that SC and its components induce apoptosis in stomach cancer cells, making it a potential candidate as a chemotherapeutic drug.

Related: Apoptosis

Chen HN, Chen XZ, Zhang WH, et al.
Necessity of harvesting at least 25 lymph nodes in patients with stage N2-N3 resectable gastric cancer: a 10-year, single-institution cohort study.
Medicine (Baltimore). 2015; 94(10):e620 [PubMed] Related Publications
A minimum of 15 lymph nodes (LNs) has been recommended as an adequate number for radical gastrectomy for gastric cancer (GC). This study aimed to investigate whether the harvesting of at least 25 LNs was a better criterion for stage N2-3 GC based on the 10-year experience of a high-volume hospital. A total of 1363 patients who underwent radical gastrectomy for gastric cancer between 2000 and 2010 were included in this study. The relationship between the number of lymph nodes examined during gastrectomy and overall survival (OS) was analyzed. In multivariate analysis, the numbers of LNs examined (P = 0.001) and N stage were confirmed as 2 of the independent prognostic factors. A larger proportion of N2/N3a/N3b patients was observed in the group with ≥20 LNs examined. The cutoff of ≥25 LNs examined exhibited a significantly lower hazard ratio (HR) than other LN cutoffs among N2-N3 diseases, but the cutoff was not significantly superior to other cutoffs in patients with N0 and N1 disease (HR, 0.64, 0.62, and 0.53 for N2, N3a, and N3b, respectively). The 5-year OS rates were 58.59% and 32.77% for N2 and N3 diseases, respectively, with ≥25 LNs examined, which represents a significant improvement over 15-24 LNs examined (52.48% and 21.67% for N2 and N3 stages, respectively). Among patients with stage N2-N3 GC, harvesting at least 25 LNs may represent a superior cutoff for radical gastrectomy and could yield better survival outcomes.

Howard JH, Hiles JM, Leung AM, et al.
Race influences stage-specific survival in gastric cancer.
Am Surg. 2015; 81(3):259-67 [PubMed] Related Publications
Gastric adenocarcinoma studies show improved survival for Asians but have not reported stage-specific overall survival (OS) or disease-specific survival (DSS) by race. The Surveillance, Epidemiology and End Results database was queried for cases of gastric adenocarcinoma between 1998 and 2008. We evaluated OS and DSS by race and stage. Number of assessed lymph nodes was compared among surgical patients. Of 49,058 patients with complete staging data, 35,300 were white, 7709 were Asian, and 6049 were black. Asians had significantly better OS for all stages (P < 0.001) and significantly better DSS for Stages I (P < 0.0001) and II (P = 0.0006). As compared with blacks, whites had significantly better DSS for Stages I (P < 0.0001), II (P = 0.0055), III (P = 0.0165), and IV (P < 0.0001). Among the 28,133 (57%) surgical patients, average number of evaluated lymph nodes was highest for Asians (P < 0.0001). Among surgical patients with 15 or more nodes evaluated, DSS was worse in blacks with Stage I disease (P < 0.05). Blacks with gastric adenocarcinoma have a worse DSS, which disappears when surgical treatment includes adequate lymphadenectomy. Race-associated survival differences for gastric adenocarcinoma might simply reflect variations in surgical staging techniques and socioeconomic factors.

Related: USA

Wang GJ, Liu GH, Ye YW, et al.
The role of microRNA-1274a in the tumorigenesis of gastric cancer: accelerating cancer cell proliferation and migration via directly targeting FOXO4.
Biochem Biophys Res Commun. 2015; 459(4):629-35 [PubMed] Related Publications
MicroRNAs (miRNAs) are a series of 18-25 nucleotides length non-coding RNAs, which play critical roles in tumorigenesis. Previous study has shown that microRNA-1274a (miR-1274a) is upregulated in human gastric cancer. However, its role in gastric cancer progression remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-1274a on gastric cancer cells. We found that miR-1274a was overexpressed in gastric cancer tissues or gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR analysis. Transfection of miR-1274a markedly promoted gastric cancer cells proliferation and migration as well as induced epithelial-mesenchymal transition (EMT) of cancer cells. Our further examination identified FOXO4 as a target of miR-1274a, which did not influence FOXO4 mRNA expression but significantly inhibited FOXO4 protein expression. Moreover, miR-1274a overexpression activated PI3K/Akt signaling and upregulated cyclin D1, MMP-2 and MMP-9 expressions. With tumor xenografts in mice models, we also showed that miR-1274a promoted tumorigenesis of gastric cancer in vivo. In all, our study demonstrated that miR-1274a prompted gastric cancer cells growth and migration through dampening FOXO4 expression thus provided a potential target for human gastric cancer therapy.

Related: MicroRNAs

Nukatsuka M, Nakagawa F, Saito H, et al.
Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, with irinotecan hydrochloride on human colorectal and gastric cancer xenografts.
Anticancer Res. 2015; 35(3):1437-45 [PubMed] Related Publications
TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5. TAS-102 was approved in Japan in March 2014 for the treatment of patients with unresectable, advanced or recurrent colorectal cancer that is refractory to standard therapies. In the present study, enhancement of the therapeutic efficacy using a combination therapy of TAS-102 and irinotecan hydrochloride (CPT-11) was evaluated in a colorectal and gastric cancer xenograft-bearing nude mouse model. TAS-102 was orally administered twice a day from day 1 to 14, and CPT-11 was administered intravenously on days 1 and 8. The growth-inhibitory activity was evaluated based on the tumor volume and the growth-delay period, which was estimated based on the period required to reach a tumor volume that was five-times greater than the initial volume (RTV5). The tumor growth-inhibitory activity and the RTV5 of the group receiving TAS-102 with CPT-11 were significantly superior to those of both agents as monotherapy for mice with KM12C, KM12C/5-FU, DLD-1/5-FU, and SC-2 xenografts (p<0.01). No significant decrease in body weight was observed. The present pre-clinical findings indicated that the combination of TAS-102 and CPT-11 is a promising treatment option for colorectal or gastric cancer, not only for chemo-naïve tumors, but also for recurrent tumors after 5-fluorouracil (5-FU)-based chemotherapy.

Related: Colorectal (Bowel) Cancer Fluorouracil Irinotecan

Hoshino I, Maruyama T, Fujito H, et al.
Detection of peritoneal dissemination with near-infrared fluorescence laparoscopic imaging using a liposomal formulation of a synthesized indocyanine green liposomal derivative.
Anticancer Res. 2015; 35(3):1353-9 [PubMed] Related Publications
BACKGROUND/AIM: Although conventional staging laparoscopy (SL) has improved the diagnostic accuracy of peritoneal dissemination, novel technology is needed to increase the sensitivity of SL. We herein describe a new imaging method employing near-infrared (NIR) fluorescence imaging using a liposomal synthesized indocyanine green (ICG) liposomal derivative, LP-ICG-C18.
METHODS AND RESULTS: LP-ICG-C18 is a NIR-photoactivating probe in which an ICG fluorophore is covalently conjugated with a phospholipid moiety. Nude mice were intraperitoneally injected with gastric cancer cells. Twelve days later, the mice were given intravenous injections of LP-ICG-C18 at a dose of 0.15 mg/kg. A NIR imaging system was used to identify the disseminated tumors. The disseminated nodules in mice were detected without any difficulties. Disseminated tumor nodules were collected from mice with or without injections of liposomal formulation and were transferred into the swine peritoneal cavity. The nodules in the swine peritoneal cavity were clearly and promptly defined by the NIR imaging system.
CONCLUSION: NIR-fluorescing liposomal probes can effectively target peritoneal disseminated tumors and can be easily detected by a NIR imaging system. These results warrant future clinical trials of our imaging system and may contribute to a more precise diagnosis and therapeutic approach for gastric cancer patients.

Kuo WT, Ho MR, Wu CW, et al.
Interrogation of microRNAs involved in gastric cancer using 5p-arm and 3p-arm annotated microRNAs.
Anticancer Res. 2015; 35(3):1345-52 [PubMed] Related Publications
MicroRNAs are derived from endogenous stem-loop precursors, and play important roles in various biological processes. From next-generation sequencing data, it is suggested that both the 5p-arm and 3p-arm of mature miRNAs could be generated from a single miRNA hairpin precursor; however, the current miRNA databases fail to provide comprehensive arm annotation features, which could result in ambiguous and incomplete analyses. In the present report, we have annotated over 99.7% of miRNAs with the correct 5p-arm and 3p-arm features. The length distribution of all annotated miRNAs is around 22 nucleotides; however, the 5p-arm miRNAs seem to be longer than those of the 3p-arm, which is evident in the 23-nucleotide group. Our study effort generates comprehensive miRNA arm-feature annotation which can be utilized for better interrogation of miRNAs. In further analysis of human gastric cancer tissues, we identified 38 down-regulated miRNAs and 22 up-regulated arm-specific miRNAs using this new comprehensives miRNA list.

Related: MicroRNAs

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