• Journal of Gastric Cancer
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• v.15 no.4
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• pp.223-230
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• 2015

Purpose: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. Materials and Methods: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. Results: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. Conclusions: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.

• Journal of Gastric Cancer
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• v.10 no.4
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• pp.212-218
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• 2010

Purpose: The aim of this study was to determine proportions of upper third gastric cancer (UTG) among all gastric cancers and analyze clinicopathological features of the disease. Materials and Methods: The medical records of 12,300 patients who underwent gastric surgery between 1986 and 2006 at Seoul National University Hospital (SNUH) were retrospectively reviewed. Clinicopathological features of 1,260 patients with UTG and 9,929 patients with middle or lower third gastric cancer (MLG) were compared, and annual proportions of UTG were evaluated. Results: The proportion of patients with UTG rapidly increased from 2.6% in 1986 to 12.5% in 1992. However, linear regression analysis showed that the rate of increase was reduced (0.21%/year) after 1992 (12.5% to 14.2% from 1992 to 2006). Compared with the MLG group, the UTG group had a lower proportion of (22.3% vs. 39.7%, P<0.001) and a greater proportion of stage III/IV disease (39.4% vs. 31.7%, P<0.001). The UTG group also had larger tumors than the MLG group in stages I/II and III (3.5 cm/5.3 cm/6.5 cm vs. 3.2 cm/5.0 cm/5.8 cm, P=0.020/0.028 /<0.001), a higher proportion of undifferentiated cancer (63.1% vs. 53.7%, P<0.001), and less intestinal Lauren's type (38.8% vs. 47.4%, P<0.001). The 5-year survival rate of the UTG group was significantly lower than that of the MLG group in stages I/II and III (85.6%/63.1%/34.2% vs. 91.6%/ 69.2%/44.7%, P<0.001/0.028/0.006). Conclusions: The proportion of UTGs has increased over the last two decades at SNUH, but the rate of increase has been greatly reduced since 1992. The UTG group showed a poorer prognosis compared with the MLG group in stages I/II and III.

• Journal of Gastric Cancer
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• v.14 no.1
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• pp.15-22
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• 2014

Purpose: To evaluate the prevalence of esophageal reflux-induced symptoms after gastrectomy owing to gastric cancer and assess the relationship between esophageal reflux-induced symptoms and quality of life. Materials and Methods: From January 2012 to May 2012, 332 patients were enrolled in this cross-sectional study. The patients had a history of curative resection for gastric cancer at least 6 months previously without recurrence, other malignancy, or ongoing chemotherapy. Esophageal reflux-induced symptoms were evaluated with the GerdQ questionnaire. The quality of life was evaluated with the European Organization for Research and Treatment QLQ-C30 and STO22 questionnaires. Results: Of the 332 patients, 275 had undergone subtotal gastrectomy and 57 had undergone total gastrectomy. The number of GerdQ(+) patients was 58 (21.1%) after subtotal gastrectomy, and 7 (12.3%) after total gastrectomy (P=0.127). GerdQ(+) patients showed significantly worse scores compared to those for GerdQ(-) patients in nearly all functional and symptom QLQ-C30 scales, with the difference in the mean score of global health status/quality of life and diarrhea symptoms being higher than in the minimal important difference. Additionally, in the QLQ STO22, GerdQ(+) patients had significantly worse scores in every symptom scale. The GerdQ score was negatively correlated with the global quality of life score (r=-0.170, P=0.002). Conclusions: Esophageal reflux-induced symptoms may develop at a similar rate or more frequently after subtotal gastrectomy compared to that after total gastrectomy, and decrease quality of life in gastric cancer patients. To improve quality of life after gastrectomy, new strategies are required to prevent or reduce esophageal reflux.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.285-293
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• 2002

Background : The lung is the most common site for a metastasis of extrapulmonary malignant tumors. however, reports on an endobronchial metastasis are rare. An endobronchial metastasis is defined as a documented extrapulmonary neoplasms metastatic to the segmental or more proximal central bronchus within a bronchoscopically visible range. The purpose of this study was to define the clinical characteristics of an endobronchial metastasis of extrapulmonary malignancies. Materials and Methods : The clinical features and treatment outcomes of 27 endobronchial metastatic cancer cases were reviewed from June, 1991 to May, 2001 in the Severance Hospital. Results : The patients' age ranged from 18 to 75. There were 17 men and 10 women. The primary tumors included the colorectum in 7, the uterine cervix in 4, the stomach and the breast in 3 patients each, and an osteosarcoma in 2 patients. The main complaint of most patients was coughing and a chest X-ray revealed a hilar mass, a parenchymal, and an atelectasis. The mean recurrence interval time was 45.5 months. The median and mean survival times were 10 and 12.3 months, respectively. Conclusion : An endobronchial metastasis is an ominous finding, and is associated with advanced-stage diseases. It requires differential diagnosis with a primary bronchogenic carcinoma. If atypical clinical features are present or an atypical cell type is discovered by a biopsy of the lesion in the lung mass, the appropriate diagnostic studies should be undertaken.

• Journal of Gastric Cancer
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• v.17 no.3
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• pp.220-227
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• 2017

Purpose: Precise localization of tumors and creation of sufficient proximal resection margins are complicated processes during total laparoscopic distal gastrectomy (TLDG) for clinical T1/T2 gastric cancers. Various solutions to this problem have also yielded many disadvantages. In this study, we reviewed a preoperative endoscopic clipping method based on the results of negative biopsy and selective intraoperative radiography. Materials and Methods: A retrospective review of 345 consecutive patients who underwent TLDG and preoperative endoscopic clipping for tumor localization was conducted. During preoperative endoscopy, the endoscopists performed negative biopsies just 1-2 cm selectively above the tumor's upper limit. After confirming the biopsy results, endoscopic metal clips were applied just proximal to the negative biopsy site the day before surgery. Selective intraoperative tumor localization using portable abdominal radiography was performed only when we could not ensure a precise resection line. Results: Negative biopsy was performed in 244 patients. Larger tumor size (P=0.008) and more distally located tumors (P=0.052) were observed more frequently in the negative biopsy group than in the non-negative biopsy group. The non-negative biopsy group had significantly higher frequencies of differentiated tumor types than the negative biopsy group (P=0.003). Of the 244 patients who underwent negative biopsies, 6 had cancer cells in their biopsy specimens. We performed intraoperative radiography in 12 patients whose tumors had difficult-to-determine proximal margins. No tumors were found in the proximal resection margins of any patients. Conclusions: Our tumor localization method is a promising and accurate method for securing a sufficient resection margin during TLDG.

• Journal of Gastric Cancer
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• v.17 no.3
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• pp.228-236
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• 2017

Purpose: Enolase is a cytoplasmic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the glycolytic pathway. The aim of this study was to investigate whether the overexpression of neuron-specific enolase (NSE) can serve as a prognostic factor in patients with gastric cancer (GC). Materials and Methods: To assess its prognostic value in GC, NSE expression was measured by immunohistochemistry in a clinically annotated tissue microarray comprising of 327 human GC specimens. Cytoplasmic NSE expression was scored from 0 to 4, reflecting the percentage of NSE-positive cells. Results: In terms of histology as per the World Health Organization criteria (P=0.34), there were no differences between the NSE overexpression (NSE-OE) and NSE underexpression (NSE-UE) groups. The NSE-OE group showed a significantly lower rate of advanced GC (P<0.01), lymph node metastasis (P=0.01), advanced stage group (P<0.01), cancer-related death (P<0.01), and cancer recurrence (P<0.01). Additionally, a Kaplan-Meier survival analysis revealed that the NSE-OE group had longer cumulative survival times than the NSE-UE group (log-rank test, P<0.01). However, there were no significant differences in the serum levels of NSE expression in patients with GC and healthy volunteers (P=0.28). Conclusions: Patients with NSE overexpressing GC tissues showed better prognostic results, implying that NSE could be a candidate biomarker of GC.

• Journal of Gastric Cancer
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• v.17 no.2
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• pp.120-131
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• 2017

Purpose: Tumor bleeding is a major complication in inoperable gastric cancer. The study aim was to investigate the effects of proton pump inhibitor (PPI) treatment for the prevention of gastric tumor bleeding. Materials and Methods: This study was a prospective double-blind, randomized, placebo-controlled trial. Patients with inoperable gastric cancer were randomly assigned to receive oral lansoprazole (30 mg) or placebo daily. The primary endpoint was the occurrence of tumor bleeding, and the secondary endpoints were transfusion requirement and overall survival (OS). Results: This study initially planned to enroll 394 patients, but prematurely ended due to low recruitment rate. Overall, 127 patients were included in the analyses: 64 in the lansoprazole group and 63 in the placebo group. During the median follow-up of 6.4 months, tumor bleeding rates were 7.8% and 9.5%, in the lansoprazole and placebo groups, respectively, with the cumulative bleeding incidence not statistically different between the groups (P=0.515, Gray's test). However, during the initial 4 months, 4 placebo-treated patients developed tumor bleeding, whereas there were no bleeding events in the lansoprazole-treated patients (P=0.041, Gray's test). There was no difference in the proportion of patients who required transfusion between the groups. The OS between the lansoprazole (11.7 months) and the placebo (11.0 months) groups was not statistically different (P=0.610). Study drug-related serious adverse event or bleeding-related death did not occur. Conclusions: Treating patients with inoperable gastric cancer with lansoprazole did not significantly reduce the incidence of tumor bleeding. However, further studies are needed to evaluate whether lansoprazole can prevent tumor bleeding during earlier phases of chemotherapy (ClinicalTrial.gov, identifier No. NCT02150447).

• Journal of Gastric Cancer
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• v.17 no.2
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.295-305
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• 2017

Purpose: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined. Materials and Methods: SMYD3 was overexpressed or suppressed by transfection with an expression plasmid or siRNA, and a wound healing migration assay and Transwell assay were performed to detect the migration and invasion ability of gastric cancer cells. Additionally, an MTT assay and clonogenic assay were performed to evaluate cell proliferation, and a cell cycle analysis was performed by propidium iodide staining. Furthermore, the expression of genes implicated in the ataxia telangiectasia mutated (ATM) pathway and proteins involved in cell cycle regulation were detected by polymerase chain reaction and western blot analyses. Results: Compared with control cells, gastric cancer cells transfected with si-SMYD3 showed lower migration and invasion abilities (P<0.05), and the absence of SMYD3 halted cells in G2/M phase and activated the ATM pathway. Furthermore, the opposite patterns were observed when SMYD3 was elevated in normal gastric cells. Conclusions: To the best of our knowledge, this study provides the first evidence that the absence of SMYD3 could inhibit the migration, invasion, and proliferation of gastric cancer cells and halt cells in G2/M phase via the ATM-CHK2/p53-Cdc25C pathway. These findings indicated that SMYD3 plays crucial roles in the proliferation, migration, and invasion of gastric cancer cells and may be a useful therapeutic target in human gastric carcinomas.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.374-383
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• 2017

Purpose: Bleeding is one of the most serious complications of advanced gastric cancer (AGC) and is associated with a poor prognosis. This study aimed to evaluate the clinical outcomes of endoscopic hemostasis for bleeding in patients with unresectable AGC. Materials and Methods: This study included 106 patients with bleeding associated with gastric cancer who had undergone endoscopic hemostasis between January 2010 and December 2013. Clinical characteristics, treatment outcomes, including rates of successful endoscopic hemostasis and rebleeding, risk factors for rebleeding, and overall survival (OS) were investigated. Results: Successful initial hemostasis was achieved in 83% of patients. Rebleeding occurred in 28.3% of patients within 30 days. The median OS after initial hemostasis was lower in patients with rebleeding than in those without rebleeding (2.7 and 3.9 months, respectively, P=0.02). There were no significant differences in disease status and rebleeding rates among patients with partial response or stable disease (n=4), progressive disease (n=64), and first diagnosis of disease (n=38). Univariate and multivariate analyses (P=0.038 and 0.034, respectively) revealed that transfusion of ${\geq}5$ units of RBCs was a significant risk factor for rebleeding. Conclusions: Despite favorable success rates of endoscopic hemostasis for bleeding associated with gastric cancer, the 30-day rebleeding rate was 28.3% and the median OS was significantly lower in patients with rebleeding than in those without rebleeding. Massive transfusion (${\geq}5$ units of RBCs) was the only significant risk factor for rebleeding. Patients with bleeding associated with AGC who have undergone massive transfusion should be observed closely following endoscopic hemostasis. Further research on approaches to reduce rebleeding rate and prevent death is needed.