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Stomach Cancer

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 (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).

Li X, Feng J, Zhang R, et al.
Quaternized Chitosan/Alginate-Fe3O4 Magnetic Nanoparticles Enhance the Chemosensitization of Multidrug-Resistant Gastric Carcinoma by Regulating Cell Autophagy Activity in Mice.
J Biomed Nanotechnol. 2016; 12(5):948-61 [PubMed] Related Publications
Multidrug resistance (MDR) and targeted therapies present major challenges in tumor chemotherapy. Nanoparticles (NPs) hold promise for use in cancer theranostics due to their advantages in terms of tumor-targeted cytotoxicity and imaging. In this study, we developed N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC)/alginate-encapsulated Fe3O4 magnetic NPs (HTCC-MNPs) and applied them to MDR gastric cancer both in vivo and in vitro. HTCC-MNPs were fabricated from sodium alginate (ALG), Fe3O4 and HTCC using an ionic gelation method. The sizes and physical characteristics of the NPs were determined using dynamic light scattering, transmission electron microscopy (TEM) and zeta potential analysis. The HTCC-MNPs exhibited excellent water solubility and biocompatibility as well as significantly reduced cell viability in the drug-resistant cancer cell line SGC7901/ADR, but not in normal gastric cells (P < 0.05). An analysis of LC3 expression demonstrated the involvement of autophagy in HTCC-MNP cytotoxicity. Additionally, apoptosis was verified using a DNA content assay. HTCC-MNPs led to mitochondrial membrane potential loss, decreased ATP production and excessive reactive oxygen species (ROS) generation compared to a control group (P < 0.05). Magnetic resonance imaging showed enrichment of HTCC-MNPs in tumor-bearing mice. In vivo bioluminescence imaging and tumor volume measurements revealed that HTCC-MNPs markedly inhibited in vivo tumor growth (P < 0.05). In conclusion, HTCC-MNPs significantly inhibited MDR gastric tumor growth and reduced tumor volume via the induction of cellular autophagy and apoptosis, which was attributed to mitochondrial dysfunction and excessive ROS accumulation.

Cainap C, Nagy V, Seicean A, et al.
Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.
J BUON. 2016 Mar-Apr; 21(2):349-59 [PubMed] Related Publications
PURPOSE: The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen.
METHODS: Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial.
RESULTS: In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS.
CONCLUSION: The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

Segura S, Pender J, Dodge J, et al.
Primary Squamous Cell Carcinoma of the Stomach: A Case Report and Review of the Literature.
Conn Med. 2016; 80(4):209-12 [PubMed] Related Publications
Primary gastric squamous cell carcinoma (PGSCC) is an exceedingly rare disease, accounting for 0.04% - 0.07% of all gastric cancers. First reported in 1895 by Rörig et al, less than 100 cases of PGSCC worldwide have been reported in the literature. These reports show PGSCC is more common in males (5:1 male to female ratio), and exhibits a peak incidence in the sixth decade of life. It may involve any portion of the stomach with predilection for the proximal stomach, especially along the lesser curvature. Although no clear pathogenesis of this tumor has been reported, several plausible theories have been proposed. These include squamous differentiation of preexisting gastric adenocarcinoma, cancerization of ectopic squamous epithelium, malignant transformation of squamous metaplasia of glandular epithelium, association with Helicobacter pylori or Epstein-Barr virus infection, and evolution in the setting of marked chronic gastritis with intestinal metaplasia. This report presents and discusses the case of a 64-year-old female who developed PGSCC arising in the gastric fundus.

Zheng D, Lin Y, Yu Y, et al.
The Value of Preoperative Neutrophil to Lymphocyte Ratio in Indicating Lymph Node Metastasis in Patients with Resectable T2 Stage Gastric Adenocarcinoma.
Clin Lab. 2016; 62(4):659-65 [PubMed] Related Publications
BACKGROUND: Lymph node metastasis (LNM) is closely associated with poor prognosis in patients with resectable T2 stage gastric adenocarcinoma (RT2-GA). Preoperative blood neutrophil to lymphocyte ratio (NLR) has been identified to be a very valuable predictor for prognosis in patients with diverse cancers. The aim of this investigation was to assess the relationship between NLR and LNM in RT2-GA.
METHODS: This retrospective study reviewed 230 patients who underwent surgery for removal of primary T2-GA from August 2002 to December 2013 in a single hospital. Preoperative routine blood test data were collected and the relationship between NLR and LNM in RT2-GA was evaluated by X2 test and multivariate logistic regression analysis.
RESULTS: The median value of NLR was 2.18 among 230 patients. Based on the median NLR value, the patients were categorized into two groups: low NLR group (NLR ≤ 2.18) and high NLR group (NLR > 2.18). χ2 test results exhibited that the preoperative NLR was significantly associated with the numbers of metastatic lymph nodes (≤ 6 and > 6) (p = 0.003) and status of lymph node involvement (N0, N1, and N2 stage) (p = 0.032). Multivariate analyses further confirmed that NLR > 2.18 was significantly associated with increased risk of appearing more numbers of metastatic lymph node or higher N stage which exhibited a 4.15- or 7.09-fold elevated risk compared to that of NLR ≤ 2.18.
CONCLUSIONS: The preoperative NLR is closely associated with LNM in patients with RT2-GA, which may be used as a predictor indicating more serious LNM in this type of cancer.

Nie X, Wang X, Lin Y, et al.
SNP rs1059234 in CDKN1A Gene Correlates with Prognosis in Resected Gastric Adenocarcinoma.
Clin Lab. 2016; 62(3):409-16 [PubMed] Related Publications
BACKGROUND: Cyclin-dependent kinase inhibitor 1A (CDKN1A) and Cyclin D1 (CCND1) play essential roles in the regulation of cell cycle progression and are closely associated with human cancer. CDKN1A and CCND1 single nucleotide polymorphisms (SNPs) have been demonstrated to influence the prognosis in humans with different cancers. However, their roles in the prognosis of patients with resected gastric adenocarcinoma (RGA) remain to be determined.
METHODS: Genotypes of CDKN1A rs1059234 and CCND1 rs603965 SNPs were performed in 235 tissue samples from RGA. The association of the genotypes of these two SNPs with the prognosis in the patients with RGA was analyzed by X2 test, multivariate Cox regression analyses, and Kaplan Meier curves.
RESULTS: During the 50 months of median follow-up time, the overall recurrence and survival rate in the whole group was 57.4% and 46.8%, respectively. Whereas, recurrence and survival rate in patients with CC genotype of rs1059234 located in 3'UTR of CDKN1A were 78.0% and 27.1% (p = 0.004; p = 0.006). Multivariate analyses further confirmed that the CC genotype was significantly related with both increased recurrence and death risk (HR 3.33, 95% CI 1.95-5.70; p = 1.07 x 10⁻⁵, and HR 3.45, 95% CI 1.95-6.10; p = 2.03 x 10⁻⁵). No significant difference among CCND1 rs603965 SNP with the prognosis was determined.
CONCLUSIONS: rs1059234 of CDKN1A is closely associated with the prognosis in patients with RGA.

Yu HH, Mi WN, Liu B, Zhao HP
In vitro and in vivo effect of paclitaxel and cepharanthine co-loaded polymeric nanoparticles in gastric cancer.
J BUON. 2016 Jan-Feb; 21(1):125-34 [PubMed] Related Publications
PURPOSE: Response surface methodology (RSM) using the central composite rotatable design (CCRD) model was used to optimize the formulation of paclitaxel (PTX)-cepharanthine (CEP) nanoparticles for gastric cancer.
METHODS: Nanoparticles were prepared using nanoprecipitation technique and optimized using central composite rotatable design response surface methodology (CCRD-RSM). Further the optimized nanoparticles were characterised for particle size (PS), zeta potential, entrapment efficiency (EE), drug loading efficiency (DL), anticancer potential against MKN45 (human gastric cancer) cells, in vivo tumor inhibition and survival analysis.
RESULTS: Significant findings were the optimal formulation of polymer concentration of 48 mg, surfactant concentration of 45% and EE of 98.12%, DL of 15.61% and mean diameter of 198±4.7 nm. The encapsulation of PTX/CEP into nanoparticles retained the synergistic anticancer efficiency against MKN45 cells. In the in vivo evaluation, PTXsCEP nanoparticles delivered into mice by intravenous injection significantly improved the antitumor efficacy of PTX/CEP. Moreover, PTX/CEP co-loaded nanoparticles substantially increased the overall survival in an established MKN45-transplanted mouse model.
CONCLUSION: These data are the first to demonstrate that PTX/CEP co-loaded nanoparticles increased the anticancer efficacy in cell lines and xenograft mouse model. Our results suggest that PTX/CEP coloaded nanoparticles could be a potential useful chemotherapeutic formulation for gastric cancer.

Zhang X, Sun F, Li S, et al.
A propensity score-matched case-control comparative study of laparoscopic and open gastrectomy for locally advanced gastric carcinoma.
J BUON. 2016 Jan-Feb; 21(1):118-24 [PubMed] Related Publications
PURPOSE: The aim of this study was to compare the surgical and long-term outcomes of laparoscopic and open gastrectomy with radical intent for locally advanced gastric carcinoma in case-controlled patient groups using the propensity score.
METHODS: Between January 2009 and December 2014, 389 patients who underwent gastrectomy with radical intent for locally advanced gastric carcinoma were enrolled. These patients were divided into two groups according to the method of operation: the laparoscopy group (patients who underwent laparoscopic gastrectomy) and the open group (patients who underwent open gastrectomy). To correct different demographic and clinical factors in the two groups, a propensity score matching was used at a 1:1 ratio, and, finally, 184 patients were enrolled in this study, 92 patients in each group. Preoperative characteristics, surgical results, and long-term results were analyzed.
RESULTS: Preoperative baseline variables were well balanced in both groups. There were no differences of the extent of surgery between the two groups. With the exception of shorter postoperative hospital stay and less blood loss in the laparoscopy group as compared with the open group, there were no significant differences in surgical, pathological, and long-term outcomes. The 5-year overall survival rates were 57% in the laparoscopy group and 50% in the open group (p=0.606). The 5-year disease-free survival rates were 48% in the laparoscopy group and 42% in the open group (p=0.515).
CONCLUSION: Laparoscopic gastrectomy for locally advanced gastric carcinoma is safe, and long-term outcomes were comparable to those who underwent open resection.

Li J, Wang SX
Synergistic enhancement of the antitumor activity of 5-fluorouracil by bornyl acetate in SGC-7901 human gastric cancer cells and the determination of the underlying mechanism of action.
J BUON. 2016 Jan-Feb; 21(1):108-17 [PubMed] Related Publications
PURPOSE: To investigate the anticancer activity of bornyl acetate and its combination with low dose 5-fluorouracil (5-FU) in human gastric cancer (SGC-7901) cells and to evaluate their effects on cell cycle, apoptosis, cancer cell morphology and DNA fragmentation.
METHODS: The anticancer activity of bornyl acetate, 5-FU and their combination against human gastric cancer (SGC-7901) cells was evaluated by MTT assay. Flow cytometry using propidium iodide (PI) as a staining agent was used to study the effect of the extract on cell cycle phase distribution. Apoptosis induced by bornyl acetate and 5-FU was evaluated by Annexin V binding assay using flow cytometer. Alterations in cell morphology following apoptosis was studied by fluorescence microscopy as well as transmission electron microscopy.
RESULTS: Bornyl acetate induced dose-dependent growth inhibitory effects on human gastric cancer cells in vitro.The combination of bornyl acetate with 5-FU induced a much more growth inhibitory effect on these cells indicating a synergistic enhancement of anticancer activity of 5-FU. The combined effect of bornyl acetate and 5-FU also resulted in greater apoptosis induction as well as cell cycle arrest in comparison to the individual treatment by bornyl acetate or 5-FU. Fluorescence microscopy as well as transmission electron microscopy also revealed that the combination of bornyl acetate with 5-FU resulted in greater apoptosis induction as well as cell morphology alterations. The percentages of early as well as late apoptotic cells were much higher in the combination treatment in comparison to separate treatment by bornyl acetate or 5-FU.
CONCLUSION: Bornyl acetate potentiates the anticancer activity of 5-FU in human gastric cancer (SGC-7901) cells by inducing apoptosis, DNA fragmentation as well as G2/M cell cycle arrest.

Shu B, Lei S, Li F, et al.
Laparoscopic total gastrectomy compared with open resection for gastric carcinoma: a case-matched study with long-term follow-up.
J BUON. 2016 Jan-Feb; 21(1):101-7 [PubMed] Related Publications
PURPOSE: This study was designed to compare the long-term outcomes of patients with gastric carcinoma after open or laparoscopic total gastrectomy.
METHODS: A case-matched controlled prospective analysis of 136 patients who underwent laparoscopic total gastrectomy for stage I-III gastric carcinoma from 2007 to 2014 was performed. Patients who at the same period underwent open total gastrectomy were matched to the laparoscopy group at the ratio of 1:1 for comparison. The perioperative clinical outcomes, postoperative pathology, and survival were compared between the 2 groups
RESULTS: The patient characteristics between the two groups were comparable. Laparoscopic resection resulted in less blood loss, shorter postoperative hospital stay, and longer operating time. The two groups had similar complication rates. Pathological data were similar for both procedures. Cumulative incidence of recurrence, disease-free, or overall survival rates were statistically similar.
CONCLUSION: This study showed that laparoscopic total gastrectomy for gastric carcinoma is acceptable in terms of short-term clinical outcomes and long-term survival results.

Chen SL, Cai SR, Zhang XH, et al.
Expression of CD4+CD25+ regulatory T cells and Foxp3 in peripheral blood of patients with gastric carcinoma.
J Biol Regul Homeost Agents. 2016 Jan-Mar; 30(1):197-204 [PubMed] Related Publications
The aim of this research was to study the clinical significance and expression of CD4+CD25+ regulatory T cells (Tregs) and p3Forkhead transcription factor-3 (Foxp3) in peripheral blood of patients with gastric carcinoma (GC) and to investigate the effects in the occurrence and development process of GC, to further comprehend their clinical values and provide a theoretical basis for the early diagnosis and immunotherapy of GC. The expression levels of CD4+CD25+Foxp3+Tregs in GC patients, at TNM staging, differentiated degree, lymphatic metastasis, cancer sites and cancer diameter of GC, were analyzed within the groups. The comparison of the expression levels of CD4+CD25+Foxp3+Tregs in peripheral blood between the GC group and the healthy control group showed a statistically significant difference. At TNM staging within the groups, pairwise comparisons of the expression levels of CD4+CD25+Foxp3+Tregs indicated that differences among the stage I+II group, stage III group and stage IV group were statistically significant. The expression levels of CD4+CD25+Foxp3+Tregs are closely relative to the occurrence and development of GC, providing theoretical bases and evidence for the early diagnosis, prognosis evaluation and immunotherapy of GC.

Best LM, Mughal M, Gurusamy KS
Laparoscopic versus open gastrectomy for gastric cancer.
Cochrane Database Syst Rev. 2016; 3:CD011389 [PubMed] Related Publications
BACKGROUND: Gastric cancer is the third most common cause of cancer-related mortality in the world. Currently there are two surgical options for potentially curable patients (i.e. people with non-metastatic gastric cancer), laparoscopic and open gastrectomy. However, it is not clear whether one of these options is superior.
OBJECTIVES: To assess the benefits and harms of laparoscopic gastrectomy or laparoscopy-assisted gastrectomy versus open gastrectomy for people with gastric cancer. In particular, we planned to investigate the effects by patient groups, such as cancer stage, anaesthetic risk, and body mass index (BMI), and by intervention methods, such as method of anastomosis, type of gastrectomy and laparoscopic or laparoscopically-assisted gastrectomy.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index, ClinicalTrials.gov and the WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) until September 2015. We also screened reference lists from included trials.
SELECTION CRITERIA: Two review authors independently selected references for further assessment by going through all titles and abstracts. Further selection was based on review of full text articles for selected references.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted study data. We calculated the risk ratio (RR) with 95% confidence interval (CI) for binary outcomes, the mean difference (MD) or the standardised mean difference (SMD) with 95% CI for continuous outcomes and the hazard ratio (HR) for time-to-event outcomes. We performed meta-analyses where it was meaningful.
MAIN RESULTS: In total, 2794 participants were randomised in 13 trials included in this review. All the trials were at unclear or high risk of bias. One trial (which included 53 participants) did not contribute any data to this review. A total of 213 participants were excluded in the remaining trials after randomisation, leaving a total of 2528 randomised participants for analysis, with 1288 undergoing laparoscopic gastrectomy and 1240 undergoing open gastrectomy. All the participants were suitable for major surgery.There was no difference in the proportion of participants who died within thirty days of treatment between laparoscopic gastrectomy (7/1188: adjusted proportion = 0.6% (based on meta-analysis)) and open gastrectomy (4/1447: 0.3%) (RR 1.60, 95% CI 0.50 to 5.10; risk difference 0.00, 95% CI -0.01 to 0.01; participants = 2335; studies = 11; I(2) = 0%; low quality evidence). There were no events in either group for short-term recurrence (participants = 103; studies = 3), proportion requiring blood transfusion (participants = 66; studies = 2), and proportion with positive margins at histopathology (participants = 28; studies = 1). None of the trials reported health-related quality of life, time to return to normal activity or time to return to work. The differences in long-term mortality (HR 0.94, 95% CI 0.70 to 1.25; participants = 195; studies = 3; I(2) = 0%; very low quality evidence), serious adverse events within three months (laparoscopic gastrectomy (7/216: adjusted proportion = 3.6%) versus open gastrectomy (13/216: 6%) (RR 0.60, 95% CI 0.27 to 1.34; participants = 432; studies = 8; I(2) = 0%; very low quality evidence), long-term recurrence (HR 0.95, 95% CI 0.70 to 1.30; participants = 162; studies = 4; very low quality evidence), adverse events within three months (laparoscopic gastrectomy (204/268: adjusted proportion = 16.1%) versus open gastrectomy (253/1222: 20.7%) (RR 0.78, 95% CI 0.60 to 1.01; participants = 2490; studies = 11; I(2) = 38%; very low quality evidence), quantity of perioperative blood transfused (SMD 0.05, 95% CI -0.27 to 0.38; participants = 143; studies = 2; I(2) = 0%; very low quality evidence), length of hospital stay (MD -1.82 days, 95% CI -3.72 to 0.07; participants = 319; studies = 6; I(2) = 83%; very low quality evidence), and number of lymph nodes harvested (MD -0.63, 95% CI -1.51 to 0.25; participants = 472; studies = 9; I(2) = 40%; very low quality evidence) were imprecise. There was no alteration in the interpretation of the results in any of the subgroups.
AUTHORS' CONCLUSIONS: Based on low quality evidence, there is no difference in short-term mortality between laparoscopic and open gastrectomy. Based on very low quality evidence, there is no evidence for any differences in short-term or long-term outcomes between laparoscopic and open gastrectomy. However, the data are sparse, and the confidence intervals were wide, suggesting that significant benefits or harms of laparoscopic gastrectomy cannot be ruled out. Several trials are currently being conducted and interim results of these trials have been included in this review. These trials need to perform intention-to-treat analysis to ensure that the results are reliable and report the results according to the CONSORT Statement.

Vrkljan AM, Grasić D, Kruljac I, et al.
Acta Clin Croat. 2015; 54(4):525-30 [PubMed] Related Publications
Autoimmune polyglandular syndrome by definition consists of two or more endocrinological insufficiencies or two organ specific autoimmune diseases. There are no stringent criteria for endocrinological evaluation of patients with one endocrine insufficiency. However, detailed endocrinological evaluation should be undertaken in patients with two autoimmune diseases. Additionally, follow up thereafter should be a must in these patients in order to avoid the possibility of not diagnosing subsequent autoimmune diseases that can occur. The aim of this case report is to point to the necessity of endocrinological screening to be made in patients presenting with gastric carcinoid type 1. We report on a 62-year-old woman who was diagnosed with primary hypothyroidism in 1993. In 2011, she was re-admitted to the hospital due to increasing fatigue. Macrocytic anemia, low vitamin B12 levels and positive parietal antibodies confirmed pernicious anemia. Furthermore, she underwent gastroscopy, which revealed two polyps in the corpus of the stomach and one in the fornix. Endoscopic mucosal resection was performed and histopathologic analysis confirmed three G1 gastric carcinoids (Ki67 2%). Additional endocrinological evaluation disclosed positive glutamic acid decarboxylase antibodies, but normal fasting and postprandial glucose and HbA1c. In 2013, she was diagnosed with glucose intolerance and subsequently with latent autoimmune diabetes of adulthood. Plasma glucose and HbA1c normalized after dietary intervention. Due to the increase of serum chromogranin A, prophylactic antrectomy was performed in 2014. The patient is still followed-up and has normal chromogranin A, gastrin and HbA1c levels.

Huang G, Chen S, Wang D, et al.
High Ki67 Expression has Prognostic Value in Surgically-Resected T3 Gastric Adenocarcinoma.
Clin Lab. 2016; 62(1-2):141-53 [PubMed] Related Publications
BACKGROUND: Antigen KI-67 (Ki67) plays a critical role in regulation of cell proliferation and has prognostic value in several types of cancer; however, the relationship between Ki67 expression and prognosis in resected T3 gastric adenocarcinoma (GA) has not yet been investigated.
METHODS: Retrospective analysis of 693 patients with T3 GA who underwent surgical resection at a single institution between July 2003 and December 2009 was performed. Ki67 expression in tumor tissues was examined using immunohistochemistry (IHC); the associations between Ki67 and prognosis/survival outcomes were assessed using the Chi-square test, Kaplan-Meier survival analysis, log-rank test, and univariate and multivariate analysis.
RESULTS: High Ki67 expression (IHC score > or = 3+) was observed in 335/693 (48.34%) of cases. Ki67 expression was significantly associated with distant metastasis, 5-year median recurrence-free survival time in months (MRFST), and 5-year median overall survival time in months (MOST). Median recurrence and overall survival were 20 and 28 months. High Ki67 expression was associated with shorter MRFST (13 vs. 27 months, p < 0.001) and MOST (21 vs. 35 months, p < 0.001 compared to low K67 expression). Multivariate analysis demonstrated that high K167 expression was an independent prognostic factor for an increased risk of recurrence (p = 0.001) and distant metastasis (p = 0.003) and poorer overall survival (p = 5.33 x 10(-5)).
CONCLUSIONS: High Ki67 expression was frequently observed in resected T3 GA and was a significant prognostic factor for poor outcome with respect to recurrence, distant metastasis and overall survival. Ki67 may represent a useful prognostic biomarker for resected T3 GA.

Wlodarczyk J, Rudnicka-Sosin L, Kużdżał J
Expression of β-catenin and its correlation with metastatic progression of esophagogastric junction adenocarcinoma.
Pol J Pathol. 2015; 66(4):414-9 [PubMed] Related Publications
The evaluation of β-catenin expression in adenocarcinoma of the esophagogastric junction and its influence on cancer progression. Sixty-one patients who were diagnosed with adenocarcinoma of the esophagogastric junction were examined. We evaluated β-catenin distribution in the cell membrane and the cell nucleus in adenocarcinoma of the esophagogastric junction type 1 and type 3. Our findings showed lack of a statistically significant difference in evaluation of adenocarcinoma type 1 and type 3 aggressiveness. However, we found a statistically significant association with the T and N stage, although we did not find an effect of them on patient survival. Patients with cellular membrane and cell nucleus staining comprise a group of patients with higher risk of malignancy progression in adenocarcinoma of the esophagogastric junction types 1 and 3.

Nonoshita T, Otsuka S, Inagaki M, Iwagaki H
Complete Response Obtained with S-1 Plus CDDP Therapy in a Patient with Multiple Liver Metastases from Gastric Cancer.
Hiroshima J Med Sci. 2015; 64(4):65-9 [PubMed] Related Publications
A 58-year-old woman with advanced gastric cancer underwent total gastrectomy in May 2012. The histological diagnosis was poorly differentiated adenocarcinoma, cT4a (SE), pN1, cM0; fStage IIIA. Chemotherapy by S-1 was started after surgery. Six months after the operation, two metastatic nodules were noticed on the liver. Therefore, the chemotherapy was switched to S-1 plus cisplatin (CDDP) in November 2012. TS-1 (80 mg/body) was administrated from day 1 to 21 followed by 14 days rest as one course. CDDP (70 mg/body) was infused on day 1. After 3 courses of this combination chemotherapy, remarkable diminution of the metastatic lesions on CT images was observed. Because of the adverse event of Grade 2 nausea, the patient was forced to discontinue chemotherapy. The patient underwent partial resection of the liver (Hr-0: S8, S7) at 1 year after the first operation. The resected specimens showed no sign of malignancy, although uneven fatty deposition was observed more frequently than in the surroundings, and designated as histologically complete response (CR). The patient has been alive 30 months after the second operation without any recurrent sites. Thus, combined use of peroral S-1 and CDDP should be recommended for multiple liver metastases after gastrectomy.

Nassoiy SP, Blackwell RH, Kothari AN, et al.
New onset postoperative atrial fibrillation predicts long-term cardiovascular events after gastrectomy.
Am J Surg. 2016; 211(3):559-64 [PubMed] Related Publications
BACKGROUND: Recent evidence suggests transient postoperative atrial fibrillation leads to future cardiovascular events, even in noncardiac surgery. The long-term effects of postoperative atrial fibrillation in gastrectomy patients are unknown.
METHODS: The Healthcare Cost and Utilization Project State Inpatient Databases identified patients undergoing gastrectomy for malignancy between 2007 and 2010. Patients were matched by propensity scores based on various factors. Adjusted Kaplan-Meier and Cox proportional hazards models assessed the effect of postoperative atrial fibrillation on cardiovascular events.
RESULTS: A higher incidence of cardiovascular events occurred over the 1st year in patients who developed postoperative atrial fibrillation. Cox proportional hazards regression confirmed an increased risk of cardiovascular events in postoperative atrial fibrillation patients.
CONCLUSIONS: Our results demonstrate that patients undergoing gastrectomy for malignancy who develop postoperative atrial fibrillation are at increased risk of cardiovascular events within 1 year. Physicians should be vigilant in assessing postoperative atrial fibrillation, given the increased risk of cardiovascular morbidity.

Matsumoto S, Takayama T, Wakatsuki K, et al.
Palliative Surgery for Gastric Cancer with Gastric Outlet Obstruction or Anemia due to Tumor Bleeding.
Hepatogastroenterology. 2015; 62(140):1041-6 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was to evaluate the surgical outcomes after palliative surgery for patients with incurable gastric cancer.
METHODOLOGY: This retrospective study included 45 patients with gastric outlet obstruction (GOO) who needed parental nutrition and 33 patients with anemia due to tumor bleeding who required blood transfusions. We compared the surgical outcomes of palliative gastrectomy (PG) and bypass surgery (BS) in each group.
RESULTS: In the GOO patients, the clinical success rate, as indicated by a resumption of an oral diet, was similar in the PG and BS groups. The time to treatment failure, when the GOO patients again required parental nutrition, was also similar between the two groups. In the anemia patients, the clinical success rate of the PG group was higher than that of BS group, and the post-operative performance status (PS) of the PG group was also better than that of the BS group, although the pre-operative PS were similar in both groups.
CONCLUSIONS: PG for the GOO patients gave little advantage compared to BS, and was associated with a longer operation, higher blood loss and more frequent complications. PG may be recommended for patients with GOO when they simultaneously have anemia due to tumor bleeding.

Miki Y, Kawamura T, Sugisawa N, et al.
Risk Classification using the Ki-67 Labeling Index for Surgically-Treated Gastric Gastrointestinal Stromal Tumors.
Hepatogastroenterology. 2015; 62(140):919-23 [PubMed] Related Publications
BACKGROUND/AIMS: Adjuvant treatment with imatinib mesylate (IM) improves survival of patients with a high risk of recurrence of gastrointestinal stromal tumors (GISTs). However, the optimal adjuvant treatment strategy remains unknown. Thus, this study aimed to identify patients who do not require adjuvant IM treatment using the Ki-67 labeling index (LI).
METHODOLOGY: The Ki-67 LI was calculated in 59 patients with gastric GISTs. A new risk classification using the Ki-67LI and tumor size was established using cut-off values determined by receiver operating characteristic analysis. This Ki-67 classification was compared with the modified Fletcher classification (MF).
RESULTS: The best cut-off values for the Ki-67LI and tumor size were 8.6% and 80 mm, respectively. According to the MF, 42, 10, and 7 patients were categorized as low, intermediate, and high risk, respectively, while the Ki-67 classification rated 38, 17, and 4 patients as low, intermediate, and high risk, respectively. The 7 patients classified as high risk by MF were graded high risk (4 patients) and intermediate risk (3 patients) by the Ki-67 classification. Recurrence was not observed in patients classed intermediate risk by the Ki-67 classification.
CONCLUSIONS: The Ki-67 classification is helpful for identifying patients for whom adjuvant IM treatment is not necessary.

Lavy R, Hershkovitz Y, Chikman B, et al.
D1 versus D2 Gastrectomy for Gastric Adenocarcinoma.
Isr Med Assoc J. 2015; 17(12):735-8 [PubMed] Related Publications
BACKGROUND: Despite the ongoing decrease in the incidence of gastric cancer, this disease is still a major cause of death. It is still debatable whether D2 lymphadenectomy improves survival and whether this procedure should be performed routinely or selectively.
OBJECTIVES: To compare the pathological and short-term results following radical D2-type gastric resection and lymphadenectomy versus the more limited D1 type resection and lymphadenectomy.
METHODS: We conducted a retrospective study on 4 years experience treating 164 patients suffering from gastric cancer. We compared the results between the group of patients who underwent a radical D2 type gastric resection and lymphadenectomy (n = 100) and those of a relatively small group of patients who intentionally underwent the more limited D1 type (n = 34).
RESULTS: The overall number of harvested lymph nodes was 9 ± 4 in the D1 group compared to 30 ± 12 (range 16-69) in the D2 group (P = 0.001). Of the 100 patients undergoing a D2 lymphadenectomy, 57% had positive nodes compared to 38% of the 34 patients in the D1 group (P = 0.045).
CONCLUSIONS: We showed statistically significant differences between D1 and D2 procedures in the overall number of harvested lymph nodes and the proportion of positive nodes to the overall number. Our results support the fact that D2 resection should be recommended as the standard approach of treatment for gastric cancer patients, ensuring a larger number of retrieved lymph nodes and a comparable rate of complications and mortality.

Zhang WH, Chen XZ, Yang K, et al.
Risk Factors and Survival Outcomes for Postoperative Pulmonary Complications in Gastric Cancer Patients.
Hepatogastroenterology. 2015; 62(139):766-72 [PubMed] Related Publications
BACKGROUND/AIMS: Facing with the high incidence rate and the poor outcomes of the postoperative pulmonary complications (PPCs), we sought to evaluate potential risk factors for developing the PPCs of gastric cancer patients.
METHODOLOGY: Retrospective study was carried out to analyze consecutive gastric cancer patients who had a preoperative pulmonary function test and underwent gastrectomy in the West China Hospital (January, 2000 - December, 2009). Potential risk factors to the development of the PPCs and the survival outcomes of these patients were also analyzed.
RESULTS: Totally, one hundred and twenty four patients (18.1%) were developed the PPCs after gastrectomy. For the development of the PPCs, univariate analysis identified the following risk factors is associated with the development of the PPCs: age ≥ 70 years (p < 0.001); male patients (p = 0.041); FEV1/FVC < 60 (p < 0.001); with the history of pulmonary disease (p < 0.001); hemoglobin < 90g/L (p = 0.025); serum albumin < 35g/L (p = 0.002); combined organoectomy (p = 0.036). Multivariate analysis identified FEV1/FVC < 60 (p = 0.004); with the history of pulmonary disease (p < 0.002); serum albumin < 35g/L (p = 0.004) were risk factors for the incidence of the PPCs.
CONCLUSIONS: For the early detection of the PPCs, extra attention should be paid to those gastric cancer patients with FEV1/FVC < 60; history of pulmonary disease and .serum albumin < 35g/L.

Yin C, Nan Y, Lu T, et al.
Clinicopathological Parameters Influence Assessment of FDG SPECT in Gastric Cancer.
Hepatogastroenterology. 2015; 62(139):762-5 [PubMed] Related Publications
BACKGROUND/AIMS: To investigate the clinicopathological parameters influencing assessment of FDG SPECT in gastric cancer.
METHODOLOGY: The frames of FDG SPECT and clinical data of 105 patients with gastric cancer were collected. The univariate and multivariate analyses were performed to assess the relationship between the visual assessment, SUV(max) and clinicopathological parameters.
RESULTS: There were statistically significant in tumor size and pT stage between the positive and negative group (p < 0.01), while there was no statistically significant in gender, age, tumor localization, pN stage, histological type, adenocarcinoma differentiation (p > 0.05). Tumor size and pT stage were independent factors associated with visual assessment at multivariate analyses (p < 0.05). SUV(max) was positively correlated with age, tumor size and pT stage, respectively (p < 0.01). There was no statistically significant of SUV(max) in gender, tumor localization, pN stage, histological type, adenocarcinoma differentiation (p > 0.05). Age, tumor size and pT stage were independent factors related to SUV(max) (p < 0.05).
CONCLUSIONS: Tumor size and depth of invasion were clinicopathological parameters influencing FDG SPECT assessment in gastric cancer independently. The relationship between tumor size, depth of invasion, expression of GLUT-1 and FDG imaging should be determined by further research.

Wang C, Wang G, Su Z, et al.
Laparoscopy-Assisted D2 Radical Gastrectomy for Advanced Gastric Cancer.
Hepatogastroenterology. 2015; 62(139):758-61 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was to investigate the efficacy and advantages of laparoscopy-assisted gastrectomy (LAG) with D2 lymphadenectomy versus conventional open D2 gastrectomy (ODG) in advanced gastric cancer (AGC) patients.
METHODOLOGY: From June 2009 to June 2014, 233 patients who were treated by conventional radical ODG and 188 cases who underwent radical LAG for AGC at our department were enrolled in this study. Clinical data recorded in hospital database was retrospectively reviewed and analyzed.
RESULTS: There were no significant differences in age, gender or preoperative laboratory tests distribution between the LAG group and the ODG group. Two (1%) of the patients who underwent LAG required conversion to ODG. The advantages of minimally invasive surgery including earlier recovery of bowel movements and shorter postoperative hospitalization time were observed in LAG group. The number of harvested lymph nodes was 24.3 ± 3.3 in the LAG group and 25.0 ± 2.8 in ODG (p = 0.110).
CONCLUSIONS: Although prospective randomized trials with long follow-up period are needed to identify the feasibility, we have shown the safety and advantages of LAG with D2 lymphadenectomy for treating AGC patients in this study.

Yamamoto M, Zaima M, Yamamoto H, et al.
Laparoscopic Total Gastrectomy for Remnant Gastric Cancer Following Distal Gastrectomy with Radical Lymphadenectomy.
Hepatogastroenterology. 2015; 62(139):752-7 [PubMed] Related Publications
BACKGROUND/AIMS: In cases of remnantgastric cancer (RGC) with previous lymphadenectomy, laparoscopic total gastrectomy (LTG) is still uncommon because of the technical difficulties associated with adhesions from previous gastric cancer surgery and variations in anastomotic reconstruction. Here we demonstrate our procedure of LTG for RGC following distal gastrectomy (DG) with radical lymphadenectomy and review its clinical results.
METHODOLOGY: From October 2008 to June 2014, we carried out three consecutive LTGs for RGC with previous lymphadenectomy. All cases had a past history of primary gastric cancer that had required open or laparoscopic DG with D2 radical lymphadenectomy. The preoperative TNM statuses of RGC were all cT1N0M0.
RESULTS: All patients successfully underwent LTG without open conversion or intraoperative complications. The median operative duration was 360 min; the median blood loss was 45 mL. The median number of retrieved lymph nodes was 23. No complications occurred postoperatively, and the median length of postoperative hospitalization was 20 days. The pathological TNM statuses of the RGC were all T1N0M0. Resection margins were negative in all cases (R0).
CONCLUSIONS: Our novel procedure of LTG for RGC following DG with radical lymphadenectomy is technically acceptable, safe, and feasible.

Huang CM, Wang Y, Wang JB, et al.
Laparoscopic Spleen-Preserving Splenic Hilar Lymph Node Dissection for Advanced Upper Gastric Cancer in Patients with High Body Mass Index.
Hepatogastroenterology. 2015; 62(139):742-7 [PubMed] Related Publications
BACKGROUND/AIMS: To evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymph node dissection for advanced upper gastric cancer in patients with high body mass index.
METHODOLOGY: Outcomes were retrospectively analyzed in 140 patients with AUGC who underwent laparoscopic spleen-preserving splenic hilar LN dissection between January 2010 and December 2012, including those with high (≥ 23 kg/m) and normal (< 23 kg/m2) BMI.
RESULTS: Except for BMI, the clinicopathologic characteristics of patients with high and normal BMI were similar. The number of retrieved No. 10 LNs per patient was significantly lower in the high than in the normal BMI group. There were no significant between group differences in operation time, blood loss, postoperative hospital stay and complications. Subgroup analysis showed that the numbers of No. 10 LNs retrieved per patient were lower in males with high than normal BMI and in patients after the initial learning curve of 40 patients with high than normal BMI.
CONCLUSIONS: Laparoscopic spleen-preserving splenic hilar LN dissection is feasible and safe in patients with high BMI, although even experienced laparoscopic surgeons should take special care in these patients, especially in men.

Liu S, Chen D, Shen W, et al.
EZH2 Mediates the Regulation of S100A4 on E-cadherin Expression and the Proliferation, Migration of Gastric Cancer Cells.
Hepatogastroenterology. 2015; 62(139):737-41 [PubMed] Related Publications
BACKGROUND/AIMS: Several reports have showed the inverse correlation between S100A4 and E-cadherin expression, but the exact molecular mechanism remained unclear. It has been reported that EZH2 mediates transcriptional silencing of E-cadherin by trimethylating lysine 27 of histone H3 (H3K27me3). Therefore, we hypothesized that EZH2 might mediate the inhibition of S100A4 on E-cadherin and further affect the functions of S100A4 in gastric cancer cells.
METHODOLOGY: RT-PCR and Western Blot were used to detect the expression of EZH2 and E-cadherin after inhibiting or increasing S100A4 expression. MTT and Transwell assay were performed to detect the proliferation and migration of gastric cancer cells.
RESULTS: Inhibition or overexpression of S100A4 led to decreased or increased EZH2 expression, and increased or decreased E-cadherin expression. The SET domain was important for EZH2 in rescuing the decreased proliferation and migration of the cells after S100A4 inhibition.
CONCLUSION: As a novel downstream target of S100A4, EZH2 mediates the inhibition of S100A4 on E-cadherin. The SET domain is important for EZH2 in mediating the cellular function of S100A4.

Jin K, Biz T, Zhou S, et al.
Totally Laparoscopic D2 Radical Distal Gastrectomy Using Delta-Shaped Anastomosis: Initial Experience.
Hepatogastroenterology. 2015; 62(139):732-6 [PubMed] Related Publications
BACKGROUND/AIMS: We presented our preliminary clinical data for totally laparoscopic D2 radical distal gastrectomy using delta-shaped anastomosis (TLG-DSA) to evaluate its effectiveness in terms of minimal invasiveness, technical feasibility, and safety for resection of early gastric cancer.
METHODOLOGY: Five consecutive patients who underwent TLG-DSA in our institution from October 22th 2013 to November 29th 2013 were enrolled in this study. In all five cases, only laparoscopic linear staplers were used for intra-corporeal anastomosis.
RESULTS: There were 3 men and 2 women, with a mean age of 67.6 years and a mean body mass index (BMI) of 21.4. All the patients with early gastric cancer were received TLG-DSA. No postoperative complications were found in all five patients, and no postoperative mortality occurred.
CONCLUSIONS: TLG-DSA using laparoscopic linear staplers for early gastric cancer was safe and feasible. Delta-shaped anastomosis is a simple, easy and safe method of intracorporeal gastroduodenostomy.

Oymaci E, Sari E, Uçar AD, et al.
Gastric Remnant Cancer: Continuing Serious and Insidious Problem for Surgeons.
Hepatogastroenterology. 2015; 62(139):727-31 [PubMed] Related Publications
BACKGROUND/AIMS: Gastric remnant cancers (GRC) are usually detected at a later stage resulting in low rates of curative resection and a consequently poor prognosis. The incidence and etiology of GRC have been changing recently because of early detection and improved outcomes in patients with gastric cancers. This study was performed to evaluate the clinicopathological characteristics and prognosis of patients with GRC.
METHODOLOGY: From January 2004 and July 2014, 27 patients with GRC who underwent surgery were analyzed retrospectively. The clinicopathological and follow-up data of 27 patients were evaluated including age, gende types of reconstruction, tumor location, histological types, TNM stages, surgical treatment and prognosis.
RESULTS: Total 221 patients underwent gastrectomy for gastric cancer and ulcer disease and 27 (12.7%) consecutive GRC patients were included in this study. The median survival for all 27 patients was 20.0 ± 2.4 months. Previous malign disease, advanced TNM stage and non-curative resection were the negative prognostic factors for survival in patients with remnant stomach cancer (p < 0.05).
CONCLUSIONS: Regular follow-up is one of the important factors affecting the early diagnosis and median survive time of patients with GRC. Curative resection is recommended operative treatment procedure to improve the survival when GRC patient diagnosed.

Noshiro H, Nomura A, Akashi M, et al.
Pure Robotic Surgery for Intraluminally Growing Gastrointestinal Stromal Tumors around the Esophagogastric junction or Pyloric Ring.
Hepatogastroenterology. 2015; 62(139):629-34 [PubMed] Related Publications
BACKGROUND/AIMS: Laparoscopic resection of gastrointestinal stromal tumors has become wide-spread as a minimally invasive surgical method. However, the limitations of laparoscopic surgery for GISTs are well recognized.
METHODOLOGY: We developed a local resection by pure robotic surgical procedure to treat intraluminally growing GISTs located in sites that are unsuitable for laparoscopic surgery. Using articulated robotic arms, the GIST is completely excised with a safe margin while employing a unique technique to provide a good operative view and to prevent the intra-abdominal dissemination of the tumor from the cut edge created by robotic excision. The defect created after excision of the tumor is closed using robotic sewing.
RESULTS: Four patients were successfully treated with pure robotic surgery without conversion to laparoscopic or open surgery or changing in the method of gastrectomy.
CONCLUSIONS: Using robotic surgery, intraluminally growing GISTs located in sites unsuitable for conventional laparoscopic surgery can be treated with minimally invasive procedures.

Matsui S, Kudo M, Kitano M, Asakuma Y
Evaluation of the Response to Chemotherapy in Advanced Gastric Cancer by Contrast-Enhanced Harmonic EUS.
Hepatogastroenterology. 2015; 62(139):595-8 [PubMed] Related Publications
BACKGROUND/AIMS: In advanced gastric cancers, a significant correlation exists between the response to chemotherapy in primary gastric cancers and patient prognosis. Therefore, accurate evaluation of the response to chemotherapy in primary gastric cancers is important. We examined the response to chemotherapy in primary gastric cancers by contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS).
METHODOLOGY: Thirty-five patients with advanced gastric cancer underwent CEH-EUS. Among these patients, 19 patients with stage IV advanced gastric cancer who received chemotherapy and CEH-EUS more than twice were enrolled, and evaluated the response to chemotherapy in primary gastric cancers by CEH-EUS and endoscopy.
RESULTS: In PRs evaluated by endoscopic findings, echo intensity ratio (EIR) was decreased, and in PDs EIR was increased significantly by CEH-EUS. Five cases had difficulty in evaluating the response of primary gastric cancers to chemotherapy by endoscopy, while evaluation was possible in those 5 cases by CEH-EUS.
CONCLUSIONS: CEH-EUS is a new method to evaluate responses to chemotherapy in primary gastric cancers not only by a change in size but also in tumor vascularity. Correct evaluation of primary gastric cancers by CEH-EUS help predicting prognosis of patients.

Tsenovski Y, Tchervenyakov A
Khirurgiia (Sofiia). 2015; 81(3):123-34 [PubMed] Related Publications
The problem of the surgical treatment of cancer of the esophagus-gastric transition is up to date until today and has caused disagreements between the surgeons. This is one of the most aggressive visceral tumors. Metastasis is very specific due to the specificity of lymph edema. We operated 213 patients for four years period, 162 of them male and 51 - female. Cancer cardia and lower third of the esophagus are seen in 163 of them. All carcinomas of the gastroesophageal transition are diagnosed as adenocarcinomas, which means there is an increase of this localization of the tumor. This distribution of cardiac carcinoma Sieber is almost equal in our series of patients. We operated 137 patients for three years period. Sieber 1 - 47 patients, Sieber 2 - 37 patients, Sieber 3 - 53 patients. The persentage raio is as follows: Sieber 1 - 34%, Sieber 2 - 27%, Sieber 3-39%.

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