• Journal of Gastric Cancer
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• v.14 no.3
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• pp.180-186
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• 2014

Purpose: At present, a human epidermal growth factor receptor 2 (HER2)-based concept of tumor biology has been established, and trastuzumab ($Herceptin^{(R)}$; Genentech/Roche, San Francisco, CA, USA), a monoclonal humanized antibody directed against HER2, is a pivotal agent for the management of HER2 positive (HER2+) metastatic breast cancer. It is also known that HER2 has a predictive value in gastric cancer; however, its association with the prognosis of this disease remains uncertain. The purpose of this study was to evaluate both the relationship between HER2 overexpression in the tumors of gastric cancer patients, and the prognosis of these patients who have had curative resection. Materials and Methods: A total of 139 consecutive patients with gastric cancer who underwent surgery at the Kosin University Gospel Hospital between October 2011 and March 2012 were included in this retrospective study. All tumor samples were examined for HER2 expression by immunohistochemistry. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Results: The HER2+ rate was 15.1%. HER2 overexpression was associated with histological grade (P=0.044) and Lauren classification (P=0.036). There was no significant difference in the 2-year overall survival between HER2+ and HER2- patients (P=0.396). Multivariate analysis showed that HER2 was not an independent prognostic factor. Conclusions: HER2 overexpression in tumors was associated with histological grade and Lauren classification in gastric cancer patients with curative resection. However, HER2 was not an independent prognostic factor for gastric cancer in our study.

• Journal of Gastric Cancer
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• v.14 no.3
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• pp.196-203
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• 2014

Purpose: Vascular endothelial growth factor (VEGF) is one of the most important growth factors for metastatic tumors. To clarify the role of VEGF-A and C in patients with peptic ulcer disease (PUD) or gastric cancer (GC), we evaluated the expression levels of these two molecules. We also analyzed the effect of Helicobacter pylori infection on VEGF-A and C expression levels. Materials and Methods: Patients with dyspepsia who needed diagnostic endoscopy were selected and divided into three groups: nonulcer dyspepsia (NUD), PUD, and GC, according to their endoscopic and histopathological results. Fifty-two patients with NUD, 50 with PUD, and 38 with GC were enrolled in this study. H. pylori infection was diagnosed by the rapid urease test. After RNA extraction and synthesis of cDNA, the expression levels of VEGF-A and C were determined by quantitative reverse transcriptase polymerase chain reaction. Results: The VEGF-C expression level in the PUD and GC groups was significantly higher than that in the NUD group. Moreover, the VEGF-A expression level in the PUD and GC groups was higher than in the NUD group, although the differences were not statistically significant. Significant positive correlations were also observed between the expression levels of these two molecules in the PUD and GC groups. In addition, the expression levels of these two molecules were higher in H. pylori positive patients with PUD or GC than in H. pylori negative patients of the same groups; however, these differences did not reach statistical significance. Conclusions: Up-regulation of VEGF-C expression during gastric mucosal inflammation may play a role in the development of peptic ulcers or GC.

• Journal of Gastric Cancer
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• v.14 no.4
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• pp.221-228
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• 2014

Purpose: This study aimed to evaluate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels to detect gastric cancer recurrence. Materials and Methods: We retrospectively reviewed 154 patients who developed recurrence within 2 years after curative gastric cancer surgery and analyzed the relationship between postoperative CEA and CA19-9 levels and recurrence. We readjusted the cut-off values to improve the detection of recurrence. Subgroup analysis according to clinicopathologic variables was performed to further investigate the relationship between recurrence and CEA and CA19-9 levels. Results: The sensitivity and specificity for elevated CEA levels to detect recurrence were 40.6% and 89.5%, respectively, and those for CA19-9 were 34.2% and 93.6%, respectively. The sensitivity and specificity for elevation of either tumor marker were 54.3% and 84.0%, respectively; those for elevation of both tumor markers were 19.2% and 98.4%, respectively. By readjusting the cut-off values from 5.0 ng/ml to 5.2 ng/ml for CEA and from 37.00 U/ml to 30.0 U/ml for CA19-9, the sensitivity was increased from 34.2% to 40.2% for CA19-9, while there was no increase in sensitivity for CEA. In subgroup analysis, the sensitivity of CEA was higher in patients with elevated preoperative CEA levels than in patients with normal preoperative CEA levels (86.7% versus 33.7%; P<0.001). Furthermore, the sensitivity of CA19-9 was higher in patients with elevated preoperative CA19-9 levels than in patients with normal preoperative CA19-9 levels (82.61% versus 26.83%; P<0.001). Conclusions: CEA and/or CA19-9 measurement with the readjusted cut-off values allows for more effective detection of gastric cancer recurrence.

• Journal of Gastric Cancer
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• v.13 no.3
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• pp.172-178
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• 2013

Purpose: The aims of this study were as follow: 1) to de scribe the expression status of estrogen receptor-${\alpha}$ and -${\beta}$ mRNAs in five gastric carcinoma cell lines; 2) to evaluate in vitro the effects of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of the cell lines. Materials and Methods: Detection of estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNA in five human gastric cancer cell lines (AGS, KATO III, MKN28, MKN45 and MKN74) was made by the reverse transcription-polymerase chain reaction system. To evaluate the effect of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of gastric cancer cell line, the cell lines which expressed both es trogen receptors were chosen and treated with $17{\beta}$-estradiol and estrogen receptor antagonists (methyl-piperidino-pyrazole and pyrazolo [1,5-a] pyrimidine). Cell proliferation was assessed with the methylthiazol tetrazolium test. Results: Estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNAs were expressed in three (KATO III, MKN28 and MKN45) and all of the five gastric cancer cell lines, respectively. At higher concentrations, $17{\beta}$-estradiol inhibited cell growth of MKN28, MKN45 and KATO III cell lines. Neither estrogen receptor-${\alpha}$ nor estrogen receptor-${\beta}$ antagonist blocked the anti-proliferative effect of $17{\beta}$-estradiol. Conclusions: Our results indicate that estrogen receptor-${\beta}$ mRNAs are preferentially expressed in gastric cancers and also imply that hormone therapy rather than estrogen receptor blockers may be a useful strategy for the treatment of estrogen receptor-${\beta}$ positive gastric cancer. Its therapeutic significance in gastric cancer are, however, limited until more evidence of the roles of estrogen receptors in the gastric cancer are accumulated.

• Journal of Gastric Cancer
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• v.16 no.3
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• pp.182-190
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• 2016

Purpose: This study aimed to establish a large-scale database of patients with gastric cancer to facilitate the development of a nationalcancer management system and a comprehensive cancer control policy. Materials and Methods: An observational prospective cohort study on gastric cancer was initiated in 2010. A total of 14 cancer centers throughout the country and 152 researchers were involved in this study. Patient enrollment began in January 2011, and data regarding clinicopathological characteristics, life style-related factors, quality of life, as well as diet diaries were collected. Results: In total, 4,963 patients were enrolled until December 2014, and approximately 5% of all Korean patients with gastric cancer annually were included. The mean age was $58.2{\pm}11.5$ years, and 68.2% were men. The number of patients in each stage was as follows: 3,394 patients (68.4%) were in stage IA/B; 514 patients (10.4%), in stage IIA/B; 469 patients (9.5%), in stage IIIA/B/C; and 127 patients (2.6%), in stage IV. Surgical treatment was performed in 3,958 patients (79.8%), endoscopic resection was performed in 700 patients (14.1%), and 167 patients (3.4%) received palliative chemotherapy. The response rate for the questionnaire on the quality of life was 95%; however, diet diaries were only collected for 27% of patients. Conclusions: To provide comprehensive information on gastric cancer for patients, physicians, and government officials, a large-scale database of Korean patients with gastric cancer was established. Based on the findings of this cohort study, an effective cancer management system and national cancer control policy could be developed.

• Journal of Gastric Cancer
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• v.13 no.2
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• pp.93-97
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• 2013

Purpose: Endoscopic submucosal dissection has recently been practiced on a differentiated type of early gastric cancer. However, there is no clear evidence for endoscopic treatments of signet ring cell carcinoma. The aim of this study is to identify the predictive clinicopathological factors for lymph node metastasis in signet ring cell carcinoma for assisting endoscopic submucosal dissection trials. Materials and Methods: A total of 186 patients with early signet ring cell carcinoma who underwent radical curative gastrectomy between January 2001 and September 2009 were enrolled in this study. Retrospective reviews of their medical records are being conducted. Several clinicopathologic factors were being investigated in order to identify predictive factors for lymph nodes metastasis: age, gender, tumor size, type of operation, tumor location, gross type, ulceration, Lauren's classification, depth of invasion, and lymphatic invasion. Results: The lymph node metastasis rate for signet ring cell carcinoma was 4.3% (n=8). Of the 186 lesions with early signet ring cell carcinoma, 91 (48.9%) tumors were larger than 15 mm in size and 40 (21.5%) showed submucosal invasions in the resection specimens. In multivariate analysis, only the lymphatic invasion (P<0.0001) showed an association with lymph node metastasis. To evaluate cutoff values for tumor sizes in the presence of lymph node metastasis, early signet ring cell carcinomas with lymphatic invasions were excluded. In the absence of lymphatic invasion, mucosal cancer with tumor sizes <15 mm had no lymph node metastasis. Conclusions: Endoscopic submucosal dissection can be performed on patients with early signet ring cell carcinoma limited to the mucosa and less than 15 mm.

• Journal of Gastric Cancer
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• v.13 no.2
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• pp.106-110
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• 2013

Purpose: We designed our study to evaluate the hypothesis that gastric cancer is correlated with iodine deficiency or thyroid dysfunction. Materials and Methods: We investigated the total body iodine reserve, thyroid function status and autoimmune disorder in 40 recently diagnosed gastric adenocarcinoma cases versus 80 healthy controls. The participants came from a region with high gastric cancer rate but sufficient iodine supply due to salt iodination. The investigation included urine iodine level, thyroid gland clinical and ultrasonographic examination, and thyroid function tests. Results: Goiter was detected more frequently in the case group (P=0.001); such a finding, however, was not true for lower than normal urine iodine levels. The free T3 mean level was significantly lower in the case group compared to the control group (P=0.005). Conclusions: The higher prevalence of goiter rather than low levels of urinary iodine in gastric adenocarcinoma cases suggests that goiter, perhaps due to protracted but currently adjusted iodine deficiency, is more likely to be associated with gastric adenocarcinoma compared to the existing iodine deficiency itself.

• Journal of Gastric Cancer
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• v.16 no.4
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• pp.221-229
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• 2016

Purpose: Dysregulated microRNAs (miRNAs) can contribute to cancer development by leading to abnormal proliferation of cells, apoptosis, and differentiation. Although several miRNAs that are related to gastric cancer have been identified, the reported results have been inconsistent. The aim of this study was to determine miRNA expression profiles and validate miRNAs up- and down-regulated in gastric cancer. Materials and Methods: We evaluated 34 primary gastric cancer tissues and paired adjacent nontumorous gastric tissues. Total RNA was extracted, and low-molecular-weight RNAs (<200 nucleotides) were isolated for further analysis. Two pairs of tissues were processed for GeneChip microarray analysis, and the identified up- and down-regulated miRNAs were validated by real-time quantitative polymerase chain reaction (qPCR). Results: In the set of differentially expressed miRNAs, 5 were overexpressed by more than 2 fold, and 5 were reduced by 2 fold or less in gastric cancer tissues compared with normal gastric tissues. Four of these miRNAs (miR-196b-5p, miR-375, miR-483-5p, and miR-486-5p) were then validated by qPCR, and the relative expression levels of 2 miRNAs (miR-196b-5p and miR-375) were significantly different between cancer and normal tissues. Conclusions: Our results revealed that the expression of miR-196b-5p and miR-375 significantly correlates with gastric cancer. These miRNAs could therefore serve as diagnostic biomarkers of gastric cancer.

• Journal of Gastric Cancer
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• v.16 no.4
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• pp.207-214
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• 2016

Purpose: The utility of N classification has been questioned after the 7th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) was published. We evaluated the correlation between ratio-based N (rN) classification with the overall survival of pathological T4 gastric cancer patients who underwent D2 lymphadenectomy. Materials and Methods: We reviewed 222 cases of advanced gastric cancer patients who underwent curative gastrectomy between January 2006 and December 2015. The T4 gastric cancer patents were classified into four groups according to the lymph node ratio (the number of metastatic lymph nodes divided by the retrieved lymph nodes): rN0, 0%; rN1, ${\leq}13.3%$; rN2, ${\leq}40.0%$; and rN3, >40.0%. Results: The rN stage showed a large down stage migration compared with pathological T4N3 (AJCC/UICC). There was a significant difference in overall survival between rN2 and rN3 groups in patients with pT4N3 (P=0.013). In contrast, the difference in metastatic lymph nodes was not significant in these patients (${\geq}16$ vs. <15; P=0.177). In addition, the rN staging system showed a more distinct difference in overall survival than the pN staging system for pathological T4 gastric cancer patients. Conclusions: Our results confirm that rN staging could be a good alternative for pathological T4 gastric cancer patients who undergo D2 lymphadenectomy. However, before applying this system to gastric cancer patients who undergo D2 lymphadenectomy, a larger sample size is required to further evaluate the usefulness of the rN staging system for all stages, including less advanced stages.

• Journal of Gastric Cancer
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• v.18 no.1
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• pp.37-47
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• 2018

Purpose: The endoscopic management of a fully covered self-expandable metal stent (SEMS) has been suggested for the primary treatment of patients with anastomotic leaks after total gastrectomy. Embedded stents due to tissue ingrowth and migration are the main obstacles in endoscopic stent management. Materials and Methods: The effectiveness and safety of endoscopic management were evaluated for anastomotic leaks when using a benign fully covered SEMS with an anchoring thread and thick silicone covering the membrane to prevent stent embedding and migration. We retrospectively reviewed the data of 14 consecutive patients with gastric cancer and anastomotic leaks after total gastrectomy treated from January 2009 to December 2016. Results: The technical success rate of endoscopic stent replacement was 100%, and the rate of complete leaks closure was 85.7% (n=12). The mean size of leaks was 13.1 mm (range, 3-30 mm). The time interval from operation to stent replacement was 10.7 days (range, 3-35 days) and the interval from stent replacement to extraction was 32.3 days (range, 18-49 days). The complication rate was 14.1%, and included a single jejunal ulcer and delayed stricture at the site of leakage. No embedded stent or migration occurred. Two patients died due to progression of pneumonia and septic shock 2 weeks after stent replacement. Conclusions: A benign fully covered SEMS with an anchoring thread and thick membrane is an effective and safe stent in patients with anastomotic leaks after total gastrectomy. The novelty of this stent is that it provides complete prevention of stent migration and embedding, compared with conventional fully covered SEMS.