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1.  The effects of laparoscopic assisted total gastrectomy on surgical outcomes in the treatment of gastric cancer 
Purpose
To evaluate the effectiveness of laparoscopic assisted total gastrectomy (LATG), we compared its early surgical outcomes with those of conventional open total gastrectomy (OTG) in patients who were diagnosed as having early gastric cancer preoperatively.
Methods
We retrospectively analyzed early surgical outcomes in 190 consecutive patients who underwent total gastrectomy for early gastric cancer between January 2009 to April 2010. The patients were divided into those who underwent LATG and those who underwent OTG. Their early surgical outcomes were analyzed to evaluate the effectiveness of LATG.
Results
There was no significant difference in postoperative complication rates (P = 0.291). But in the analysis of other early surgical outcomes, we found that LATG could improve time to first flatus (P < 0.001), time to commencement of soft diet (P = 0.034), administration of analgesics (P = 0.024), pain score (Numeric Rating Scale), and hospital discharge (P = 0.045).
Conclusion
Although LATG didn't show better results for postoperative complications than those of OTG, LATG contributes to the improvement of early surgical outcomes, including bowel movement, pain score and hospital discharge. Therefore, we suggest that LATG could be a method to improve early surgical outcomes in patients who need total gastrectomy.
doi:10.4174/jkss.2011.80.4.245
PMCID: PMC3204674  PMID: 22066043
Early gastric cancer; Laparoscopic assisted total gastrectomy; Open total gastrectomy
2.  ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population 
AIM: To evaluate the association between the genetic polymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.
METHODS: The study subjects were 477 age- and sex-matched case-control pairs. Genotyping was performed for 15 single nucleotide polymorphisms (SNPs) in ITGA1. The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models. Multiple testing corrections were carried out following methodology for controlling the false discovery rate. Gene-based association tests were performed using the versatile gene-based association study (VEGAS) method.
RESULTS: In the codominant model, the ORs for SNPs rs2432143 (1.517; 95%CI: 1.144-2.011) and rs2447867 (1.258; 95%CI: 1.051-1.505) were statistically significant. In the dominant model, polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors, with ORs of 1.337 (95%CI: 1.029-1.737) and 1.412 (95%CI: 1.061-1.881), respectively. In the recessive model, only the rs2432143 polymorphism was significant (OR = 1.559, 95%CI: 1.150-2.114). The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model (OR = 0.602, 95%CI: 0.212-0.709, P = 0.021) and the dominant model (OR = 0.653, 95%CI: 0.483-0.884). The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test. In the dominant model, the A-T type of ITGA1 haplotype block 2 was a significant risk factor (OR = 1.341, 95%CI: 1.034-1.741). SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and, thus, to the risk of developing gastric cancer.
CONCLUSION: ITGA1 gene SNPs rs1862610, rs24321
43, and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.
doi:10.3748/wjg.v19.i35.5870
PMCID: PMC3793141  PMID: 24124332
Integrin; ITGA1; Gastric cancer; Polymorphism; Haplotype
3.  Evaluation of the relationship between dietary factors, CagA-positive Helicobacter pylori infection, and RUNX3 promoter hypermethylation in gastric cancer tissue 
AIM: To evaluate the relationship among Helicobacter pylori (H. pylori) infection, CagA status, and dietary factors with RUNX3 promoter hypermethylation.
METHODS: Gastric cancer tissue samples were collected from 184 South Korean patients. All patients were interviewed following a semi-quantitative food frequency questionnaire. The average frequencies of intake and portion sizes of 89 common food items were documented, and total intakes of calories, nutrients, vitamins, and minerals were calculated for each subject. DNA was extracted from gastric cancer tissue samples, and amplification of the HSP60 gene was performed to detect H. pylori infection. Nested polymerase chain reaction (PCR) was used to detect the presence of the CagA gene. RUNX3 gene expression was measured by reverse transcription-PCR, and RUNX3 methylation status was evaluated by methylation-specific PCR. The odds ratios (ORs) and 95%CI associated with RUNX3 promoter hypermethylation status were estimated for each of the food groups, lifestyle factors, and the interaction between dietary and lifestyle factors with CagA status of H. pylori infection.
RESULTS: Overall, 164 patients (89.1%) were positive for H. pylori DNA, with the CagA gene detected in 59 (36%) of these H. pylori-positive samples. In all, 106 (57.6%) patients with gastric cancer demonstrated CpG island hypermethylation at the RUNX3 promoter. RUNX3 expression was undetectable in 52 (43.7%) of the 119 gastric cancer tissues sampled. A high consumption of eggs may increase the risk of RUNX3 methylation in gastric cancer patients, having a mean OR of 2.15 (range, 1.14-4.08). A significantly increased OR of 4.28 (range, 1.19-15.49) was observed with a high consumption of nuts in patients with CagA-positive H. pylori infection. High intakes of carbohydrate, vitamin B1, and vitamin E may decrease the risk of RUNX3 methylation in gastric cancer tissue, particularly in CagA- or H. pylori-negative infection, with OR of 0.41 (0.19-0.90), 0.42 (0.20-0.89), and 0.29 (0.13-0.62), respectively. A high consumption of fruits may protect against RUNX3 methylation.
CONCLUSION: These results suggest that the CagA status of H. pylori infection may be a modifier of dietary effects on RUNX3 methylation in gastric cancer tissue.
doi:10.3748/wjg.v19.i11.1778
PMCID: PMC3607754  PMID: 23555166
Gastric cancer; RUNX3; Helicobacter pylori; CagA; Dietary factors
4.  Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study 
Background
Mistletoe (Viscum album L.) extracts are widely used in complementary cancer therapy. Aim of this study was to evaluate safety and efficacy of a standardized mistletoe extract (abnobaVISCUM® Quercus, aVQ) in patients with gastric cancer.
Patients and Methods
32 operated gastric cancer patients (stage Ib or II) who were waiting for oral chemotherapy with the 5-FU prodrug doxifluridine were randomized 1:1 to receive additional therapy with aVQ or no additional therapy. aVQ was injected subcutaneously three times per week from postoperative day 7 to week 24 in increasing doses. EORTC QLQ-C30 and -STO22 Quality of Life questionnaire, differential blood count, liver function tests, various cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)-2), CD 16+/CD56+ and CD 19+ lymphocytes were analyzed at baseline and 8, 16 and 24 weeks later.
Results
Global health status (p <0.01), leukocyte- and eosinophil counts (p ≤0.01) increased significantly in the treatment group compared to the control group. Diarrhea was less frequently reported (7% vs. 50%, p=0.014) in the intervention group. There was no significant treatment effect on levels of TNF-alpha, IL-2, CD16+/CD56+ and CD 19+ lymphocytes and liver function tests measured by ANOVA.
Conclusion
Additional treatment with aVQ is safe and was associated with improved QoL of gastric cancer patients. ClinicalTrials.Gov Registration number NCT01401075.
doi:10.1186/1472-6882-12-172
PMCID: PMC3488325  PMID: 23033982
Qol; EORTC QLQ-C30; QLQ-STO22; 5-FU; Viscum album
5.  Effects of Dietary Factors and the NAT2 Acetylator Status on Gastric Cancer in Koreans 
Environmental dietary carcinogens and genetic polymorphisms in metabolic enzymes have been reported to be risk factors for gastric cancer. This study was undertaken to investigate the effects of the diet, the N-acetyltransferase (NAT) 2 acetylation status, and their interaction on gastric cancer risk. The study population consisted of 471 gastric cancer patients and 471 age- and sex-matched control subjects. NAT2 genotypes were identified using single-nucleotide primer extension reaction methods. Thirty-one alleles related to 12 polymorphism sites were assayed in this study. Significantly increased odds ratios were observed in former smokers (OR = 2.39, 95%CI = 1.57-3.62), heavy drinkers (OR = 1.28, 95%CI = 1.06-1.55), and individuals who eat well-done meat (OR = 1.24, 95%CI = 1.09-1.41). The odds ratios (95% CI) for high intake of kimchi, stews, and soybean paste were 3.27 (2.44-4.37), 1.96 (1.50-2.58), and 1.63 (1.24-2.14), respectively. The NAT2 genotype alone was not associated with gastric cancer risk. A significant gene-environment interaction was observed between environmental carcinogens and NAT2 genotypes. The odds ratios for kimchi, stews, and soybean paste were higher in slow/intermediate acetylators than in rapid acetylators. The odds ratios for slow/intermediate acetylators were 2.28 (95% CI: 1.29-4.04) for light smokers and 3.42 (95% CI: 2.06-5.68) for well-done meat intake. The NAT2 acetylator genotype may be an important modifier of the effects of environmental factors on gastric cancer risk.
doi:10.1002/ijc.24328
PMCID: PMC2766547  PMID: 19350634
gastric cancer; N-acetyltransferase 2; genotype; dietary factor
6.  Efficacy and Safety Study of Docetaxel as Salvage Chemotherapy in Metastatic Gastric Cancer Failing Fluoropyrimidine and Platinum Combination Chemotherapy 
Purpose
Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the first line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease. The present study retrospectively investigated the efficacy of D monotherapy as salvage chemotherapy for AGC that is failing F and P combination chemotherapy.
Materials and Methods
A total of 34 patients, fitting the eligibility criteria, were included in this study. D was administered at a dose of 75 mg/m2 IV every 3 weeks, with dexamethasone prophylaxis. Twenty-nine patients had measurable lesions. The median treatment-free interval was 38.5 days, and 91.2% of patients had progressed within 4 months of withdrawal of the first line chemotherapy.
Results
A total of 133 cycles of D were administered, with a median of 3.5 (1~8) cycles. From an intention-to-treat analysis, 6 patients achieved partial responses (PR), with a response rate of 20.7% (95% CI, 6.0~35.4). The duration of objective PRs in these six were 2.3+, 2.5+, 2.9, 3.0+, 6.2 and 6.8 months, respectively. Six patients showed a stable disease, but 15 showed progression. The median time to progression was 4.2 months (95% CI, 2.8~5.5), with a median overall survival since the start of D monotherapy of 8.4 months (95% CI, 5.5~11.3). Grade 3/4 neutropenia and febrile neutropenia occurred in 12.9% of patients and 3.1% of cycles. The incidence of grade 3 or worse non-hematological toxicities were as follows; peripheral sensory neuropathy 9.7%, asthenia 3.2% and allergic reaction 2.7%.
Conclusion
Docetaxel, 75 mg/m2, is active in AGC as second-line chemotherapy after failure of prior exposure to the F and P combination chemotherapy, with a favorable toxicity profile.
doi:10.4143/crt.2005.37.4.201
PMCID: PMC2785917  PMID: 19956514
Stomach neoplasms; Docetaxel; Salvage therapy; Drug therapy
7.  Clinicopathological Analysis of Borrmann Type IV Gastric Cancer 
Purpose
Borrmann type IV gastric cancer is often diagnosed only at an advanced stage, resulting in a prognosis poor. We performed a retrospective study of the clinical characteristics of Borrmann type IV gastric cancer and the prognostic factors affecting the survival rate in such patients.
Materials and Methods
Of 4,063 patients with all gastric cancers, 370 (9%) with Borrmann type IV gastric cancer were analyzed.
Results
The clinical characteristics of these patients included a higher incidence rate in young females, and higher rates of serosa exposure, metastasis to lymph nodes and early peritoneal dissemination. Of patients presenting with peritoneal seeding, those resected had a higher survival rate than those that were not. A univariate analysis showed that the prognostic factors affecting the survival rate following a curative resection were the location, occupied area and depth of the primary tumor, as well as the presence of lymph node metastasis and the tumor stage. A multivariate analysis indicated that the tumor location and stage were significant independent prognostic factors after a curative resection for Borrmann type IV gastric cancer.
Conclusion
In conclusion, the early diagnosis and treatment of patients with Borrmann type IV gastric cancer are essential for the better survival of these patients. Even in patients with advanced tumors, a noncurative palliative resection may improve the prognosis.
doi:10.4143/crt.2005.37.2.87
PMCID: PMC2785394  PMID: 19956485
Borrmann type IV; Stomach neoplasms
8.  Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors of the Stomach: Report of Three Cases 
Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.
doi:10.4143/crt.2006.38.3.178
PMCID: PMC2741673  PMID: 19771279
Gastrointestinal stromal tumors; Imatinib; Neoadjuvant therapy; Surgery

Results 1-8 (8)