• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1057-1060
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• 2016

Background: The tumor suppressor p53 is as a regulator of cell proliferation, apoptosis and many other biological processes as well as external and internal stress responses. Mdm2 SNIP309 is a negative regulator of 53. Therefore, this study aimed to determine the role of the Mdm2 SNIP 309 polymorphism in the gastric mucosal morphological patterns in patients with Helicobacter pylori associated gastritis. Materials and Methods: A prospective cross-sectional study was carried out from November 2014 through November 2015. Biopsy specimens were obtained from patients and infection was proven by positive histology. Gastric mucosa specimens were sent to the Molecular Genetics Unit, Institute of Medicine, Suranaree University of Technology where they were tested by molecular methods to detect the patterns of Mdm2 SNIP 309 polymorphism using the real-time PCR hybridization probe method. The results were analyzed and correlated with gastric mucosal morphological patterns by using C-NBI endoscopy. Results: A total of 300 infected patients were enrolled and gastric mucosa specimens were collected. In this study the percentage of Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygous was 78% and 19 % respectively whereas Mdm2 SNIP309 G/G homozygous was 3%. Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygosity correlated with type 1 to type 3 gastric mucosal morphological patterns (P<0.01) whereas Mdm2 SNIP309 G/G homozygous correlated with type 4 and type 5 (P<0.01). Conclusions: Our study finds the frequency of Mdm2 SNIP309 G/G in a Thai population is very low, and suggests that this can explain ae Thailand enigma. Types 1 to type 3 are the most common gastric mucosal morphological patterns according to the unique genetic polymorphism of MDM2 SNIP 309 in the Thai population.

• Molecules and Cells
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• 제41권6호
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• pp.532-544
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• 2018

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

• Journal of Gastric Cancer
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• 제13권3호
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• pp.164-171
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• 2013

Purpose: Laparoscopy-assisted distal gastrectomy for early gastric cancer has gained acceptance and popularity worldwide. However, laparoscopy-assisted distal gastrectomy for advanced gastric cancer is still controversial. Therefore, we propose this prospective randomized controlled multi-center trial in order to evaluate the safety and feasibility of laparoscopy assisted D2-gastrectomy for advanced stage gastric cancer. Materials and Methods: Patients undergoing distal gastrectomy for advanced gastric cancer staged cT2/3/4 cN0/1/2/3a cM0 by endoscopy and computed tomography are eligible for enrollment after giving their informed consent. Patients will be randomized either to laparoscopyassisted distal gastrectomy or open distal gastrectomy. Sample size calculation revealed that 102 patients are to be included per treatment arm. The primary endpoint is the non-compliance rate of D2 dissection; relevant secondary endpoints are three-year disease free survival, surgical and postoperative complications, hospital stay and unanimity rate of D2 dissection evaluated by reviewing the intraoperative video documentation. Discussion: Oncologic safety is the major concern regarding laparoscopy-assisted distal gastrectomy for advanced gastric cancer. Therefore, the non-compliance rate of clearing the N2 area was chosen as the most important parameter for the technical feasibility of the laparoscopic procedure. Furthermore, surgical quality will be carefully reviewed, that is, three independent experts will review the video records and score with a check list. For a long-term result, disease free survival is considered a secondary endpoint for this trial. This study will offer promising evidence of the feasibility and safety of Laparoscopy-assisted distal gastrectomy for advanced gastric cancer. Trial Registration: NCT01088204 (international), NCCCTS-09-448 (Korea).

• Journal of Gastric Cancer
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• 제16권2호
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• pp.85-92
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• 2016

Purpose: PIK3CA is often mutated in a variety of malignancies, including colon, gastric, ovary, breast, and brain tumors. We investigated PIK3CA expression in gastric cancer and explored the relationships between the PIK3CA expression level and clinicopathological features as well as survival of the patients. Materials and Methods: We examined PIK3CA expression in a tissue microarray of 178 gastric adenocarcinomas by immunohistochemistry and reviewed patients' medical records. Results: In our study, 112 of the 178 gastric cancer patients displayed positive PIK3CA expression. Overexpression of PIK3CA was correlated with low grade differentiation (P=0.001), frequent lymphatic invasion (P=0.032), and high T stage (P=0.040). Patients with positive PIK3CA staining were more likely to display worse overall survival rate than those with negative PIK3CA staining, as determined by Kaplan-Meier survival analysis with log-rank test (P=0.047) and a univariate analysis using the Cox proportional hazard model (hazard ratio=1.832, P=0.051). Conclusions: Elevated PIK3CA expression was significantly correlated with tumor invasiveness, tumor phenotypes, and poor patient survival.

• Journal of Gastric Cancer
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• 제20권4호
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• pp.431-441
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• 2020

Purpose: Various studies have indicated that reduced-port robotic gastrectomies are safe and feasible for treating patients with early gastric cancer. However, there have not been any comparative studies conducted that have evaluated patients with clinically advanced gastric cancer. Therefore, we aimed to compare the perioperative outcomes of D2 lymph node dissections during reduced-port robotic distal subtotal gastrectomies (RRDGs) and conventional 5-port laparoscopic distal subtotal gastrectomies (CLDGs). Materials and Methods: We retrospectively evaluated 118 patients with clinically advanced gastric cancer who underwent minimally invasive distal subtotal gastrectomies with D2 lymph node dissections between February 2016 and November 2019. To evaluate the patient data, we performed a 1:1 propensity score matching (PSM) according to age, sex, body mass index, American Society of Anesthesiologists physical status classification score, and clinical T status. The short-term surgical outcomes were also compared between the two groups. Results: The PSM identified 40 pairs of patients who underwent RRDG or CLDG. The RRDG group experienced a significantly longer operation time than the CLDG group (P<0.001), although the RRDG group had significantly less estimated blood loss (P=0.034). The number of retrieved extraperigastric lymph nodes in the RRDG group was significantly higher than that of the CLDG group (P=0.008). The rate of postoperative complications was not significantly different between the two groups (P=0.115). Conclusions: D2 lymph node dissections can be safely performed during RRDGs and the perioperative outcomes appear to be comparable to those of conventional laparoscopic surgeries. Further studies are needed to compare long-term survival outcomes.

• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.3015-3020
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• 2016

Background: Numerous studies have investigated associations of DNA methyltransferase (DNMT) -149 C>T and -579 G>T polymorphisms with gastric cancer (GC) and colorectal cancer (CRC) susceptibility; however, the findings are inconsistent prompting the present meta-analysis. Materials and Methods: Related studies were identified from PubMed, Google scholar, and SID until 10 October 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. Results: Eleven studies were included based on the search criteria for CRC and GC related to the DNMT3B 149 C>T (3,353 cases and 4,936 controls) and DNMT3B 579 G>T (1,387 cases and 2,064 controls) polymorphisms. There was no significant association overall between DNMT3B -149 and 579 polymorphisms and the risk of cancer. In the stratified analysis by cancer type, DNMT3B 579G>T polymorphism was associated with the risk of CRC and GC. While the DNMT3B -149C/T polymorphism was related with a significantly increased risk of CRC in two tested models, dominant (GG+GT vs. TT: OR 0.51, 95 % CI 0.38-0.69; P = 0.00, Pheterogeneity=0.69, $I^2=0%$) and heterozygote (GT vs. TT: OR 0.50, 95 % CI 0.37-0.69; P=0.00, Pheterogeneity=0.41, $I^2=0%$), no evidence of any association with GC risk was observed as in the pooled analyses. Conclusions: More studies are needed to assess associations of DNMT3B -149C/T and DNMT3B 579G>T polymorphisms with cancer in different ethnicities with large population sizes to generate comprehensive conclusions.

• Journal of Gastric Cancer
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• 제18권4호
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• pp.348-355
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• 2018

Purpose: We aimed to discuss the roles of radiation and chemotherapy as adjuvant treatment in patients with staged IB GC who were enrolled in the adjuvant chemoradiotherapy in stomach tumors (ARTIST) trial. Materials and Methods: Among the 458 patients who were enrolled in the ARTIST trial, 99 had stage IB disease. The patients were randomly assigned to receive either adjuvant chemoradiotherapy with capecitabine plus cisplatin (XP, n=50) or chemoradiotherapy (XPRT, n=49). Survival analyses were performed in accordance with the AJCC 2010 staging system. Results: According to the AJCC 2010 system, stage migration from IB to II occurred in 71% of the patients; 98% of the T2 N0 cases were reclassified as T3 N0, and 42% of the T1 N1 cases were reclassified as T1 N2. When comparing survival outcomes between the XPRT and XP arms for stage IB cancer (AJCC 2002), no significant difference in 5-year disease-free survival (DFS) between the 2 arms was found. (median 5-year DFS, not reached, P=0.256). The patients classified as having stage IB cancer (AJCC 2002) and reclassified as having stage II cancer (AJCC 2010) exhibited worse prognoses than those who remained in stage IB, although the difference was not statistically significant (5-year DFS rate, 83% vs. 93%). When we compared 5-year DFS in 70 patients with stage II (AJCC 2010), the addition of radiotherapy to XP chemotherapy did not show better outcome than XP alone (P=0.137). Conclusions: The role of adjuvant chemoradiotherapy in the treatment of stage IB GC (AJCC 2002) warrants further investigation.

• Journal of Gastric Cancer
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• 제17권1호
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• pp.21-32
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• 2017

Purpose: Perioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer. Materials and Methods: We retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai. Results: Among the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival. Conclusions: EOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resections, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial.

• Journal of Gastric Cancer
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• 제19권4호
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• pp.427-437
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• 2019

Purpose: We aimed to evaluate the clinical characteristics of microsatellite instability in early gastric cancer. Materials and Methods: The microsatellite instability status of resected early gastric tumors was evaluated using two mononucleotide repeat markers (BAT25 and BAT26) and three dinucleotide repeat markers (D5S346, D2S123, and D17S250). Tumors with instability in two or more markers were defined as microsatellite instability-high (MSI-H) and others were classified as microsatellite stable (MSS). Results: Overall, 1,156 tumors were included in the analysis, with 85 (7.4%) classified as MSI-H compared with MSS tumors. For MSI-H tumors, there was a significant correlation with the female sex, older age, tumor location in the lower gastric body, intestinal histology, lymphovascular invasion (LVI), and submucosal invasion (P<0.05). There was also a trend toward an association with lymph node (LN) metastasis (P=0.056). In mucosal gastric cancer, there was no significant difference in MSI status in tumors with LN metastasis or tumors with LVI. In submucosal gastric cancer, LVI was more frequently observed in MSI-H than in MSS tumors (38.9% vs. 25.0%, P=0.027), but there was no difference in the presence of LN metastases. The prognosis of MSI-H tumors was similar to that of MSS tumors (log-rank test, P=0.797, the hazard ratio for MSI-H was adjusted by age, sex, pT stage, and the number of metastatic LNs, 0.932; 95% confidence interval, 0.423-2.054; P=0.861). Conclusions: MSI status was not useful in predicting prognosis in early gastric cancer. However, the frequent presence of LVI in early MSI-H gastric cancer may help guide the appropriate treatment for patients, such as endoscopic treatment or limited LN surgical dissection.

• Journal of Gastric Cancer
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• 제15권3호
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• pp.209-213
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• 2015

A 78-year-old man underwent laparoscopy-assisted total gastrectomy for gastric cancer (pT3N0M0). Multiple port sites were used, including a 10 mm port for a videoscope at the umbilical point and three other working ports. During the six-month follow-up evaluation, a 2 cm enhancing mass confined to the muscle layer was found 12 mm from the right lower quadrant port site, suggesting a metastatic or desmoid tumor. Follow-up computed tomography imaging two months later showed that the mass had increased in size to 3.5 cm. We confirmed that there was no intra-abdominal metastasis by diagnostic laparoscopy and then performed a wide resection of the recurrent mass. The histologic findings revealed poorly differentiated adenocarcinoma, suggesting a metastatic mass from the stomach cancer. The postoperative course was uneventful, and the patient completed adjuvant chemotherapy with TS-1 (tegafur, gimeracil, and oteracil potassium). There was no evidence of tumor recurrence during the 50-month follow-up period.