• Journal of Gastric Cancer
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• v.5 no.2
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• pp.113-119
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• 2005

Purpose: Some controversies exist over the prognostic values of lymphatic, venous, and neural invasion in patients with gastric cancer. This study was conducted to confirm the prognostic values of these histopathologic factors in gastric cancer patients who received a gastrectomy. Materials and Methods: Data for clinicopathologic factors and clinical outcomes were collected retrospectively from the medical records of 1,018 gastric cancer patients who received a gastrectomy at Yeungnam University Medical Center between January 1995 and December 1999. A statistical analysis was done using the SPSS program for Windows (Version 10.0, SPSS Inc., USA). The Kaplan-Meier method was used for the survival analysis. Prognostic factors were analyzed by using a multivariate analysis with Cox proportional hazard regression model. Results: Ages ranged from 21 to 79 (median age, 56). A univariate analysis revealed that age, tumor size, location, gross type, depth of invasion, extent of gastrectomy or lymph node dissection, lymph node metastasis, distant metastasis, lymphatic invasion, venous invasion, neural invasion, pathologic stage, histologic type, and curability of surgery had statistical significance. Among these factors, lymph node metastasis, curability of surgery, neural invasion, lymphatic invasion, and depth of invasion were found to be independent prognostic factors by using a multivariate analysis. Venous invasion showed no prognostic value in the multivariate analysis. Conclusion: Neural invasion and lymphatic invasion are useful parameters in determining a prognosis for gastric cancer patients.

• Journal of Gastric Cancer
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• v.12 no.4
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• pp.210-216
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• 2012

Purpose: To assess independent prognostic factors for lymph node-negative metastatic gastric cancer patients following curative resection is valuable for more effective follow-up strategies. Materials and Methods: Among 1,874 gastric cancer patients who received curative resection, 967 patients were lymph node-negative. Independent prognostic factors for overall survival in lymph node-negative gastric cancer patients grouped by tumor invasion depth (early gastric cancer versus advanced gastric cancer) were explored with univariate and multivariate analyses. Results: There was a significant difference in the distribution of recurrence pattern between lymph node-negative and lymph nodepositive group. In the lymph node-negative group, the recurrence pattern differed by the depth of tumor invasion. In univariate analysis for overall survival of the early gastric cancer group, age, macroscopic appearance, histologic type, venous invasion, lymphatic invasion, and carcinoembryonic antigen level were significant prognostic factors. Multivariate analysis for these factors showed that venous invasion (hazard ratio, 6.695), age (${\geq}59$, hazard ratio, 2.882), and carcinoembryonic antigen level (${\geq}5$ ng/dl, hazard ratio, 3.938) were significant prognostic factors. Multivariate analysis of advanced gastric cancer group showed that depth of tumor invasion (T2 versus T3, hazard ratio, 2.809), and age (hazard ratio, 2.319) were prognostic factors on overall survival. Conclusions: Based on our results, independent prognostic factors such as venous permeation, carcinoembryonic antigen level, and age, depth of tumor invasion on overall survival were different between early gastric cancer and advanced gastric cancer group in lymph node-negative gastric cancer patients. Therefore, we are confident that our results will contribute to planning follow-up strategies.

• Journal of Gastric Cancer
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• v.16 no.3
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• pp.161-166
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• 2016

Purpose: Lymph node (LN) metastasis is the best prognostic indicator in non-distant metastatic advanced gastric cancer. This study aimed to assess the prognostic value of various clinicopathologic factors in node-negative advanced gastric cancer. Materials and Methods: We retrospectively analyzed the clinical records of 254 patients with primary node-negative stage T2~4 gastric cancer. These patients were selected from a pool of 1,890 patients who underwent radical resection at Memorial Jin-Pok Kim Korea Gastric Cancer Center, Inje University Seoul Paik Hospital between 1998 and 2008. Results: Of the 254 patients, 128 patients (50.4%), 88 patients (34.6%), 37 patients (14.6%), and 1 patient (0.4%) had T2, T3, T4a, and T4b tumors, respectively. In a univariate analysis, operation type, T-stage, venous invasion, tumor size, and less than 15 LNs significantly correlated with tumor recurrence and cumulative overall survival. In a multivariate logistic regression analysis, tumor size, venous invasion, and less than 15 LNs significantly and independently correlated with recurrence. In a multivariate Cox proportional hazards analysis, tumor size (hazard ratio [HR]: 2.926; 95% confidence interval [CI]: 1.173~7.300; P=0.021), venous invasion (HR: 3.985; 95% CI: 1.401~11.338; P=0.010), and less than 15 LNs (HR: 0.092; 95% CI: 0.029~0.290; P<0.001) significantly correlated with overall survival. Conclusions: Node-negative gastric cancers recurred in 8.3% of the patients in our study. Tumor size, venous invasion, and less than 15 LNs reliably predicted recurrence as well as survival. Aggressive postoperative treatments and timely follow-ups should be considered in cases with these characteristics.

• Molecules and Cells
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• v.40 no.5
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• pp.346-354
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• 2017

Long interspersed nuclear element-1 (LINE-1) is a retrotransposon that contains a CpG island in its 5'-untranslated region. The CpG island of LINE-1 is often heavily methylated in normal somatic cells, which is associated with poor prognosis in various cancers. DNA methylation can differ between formalin-fixed paraffin-embedded (FFPE) and frozen tissues. Therefore, this study aimed to compare the LINE-1 methylation status between the two tissue-storage conditions in gastric cancer (GC) clinical samples and to evaluate whether LINE-1 can be used as an independent prognostic marker for each tissue-storage type. We analyzed four CpG sites of LINE-1 and examined the methylation levels at these sites in 25 FFPE and 41 frozen GC tissues by quantitative bisulfite pyrosequencing. The LINE-1 methylation status was significantly different between the FFPE and frozen GC tissues (p < 0.001). We further analyzed the clinicopathological features in the two groups separately. In the frozen GC tissues, LINE-1 was significantly hypomethylated in GC tissues compared to their corresponding normal gastric mucosa tissues (p < 0.001), and its methylation status was associated with gender, differentiation state, and lymphatic and venous invasion of GC. In the FFPE GC tissues, the methylation levels of LINE-1 differed according to tumor location and venous invasion of GC. In conclusion, LINE-1 can be used as a useful methylation marker for venous invasion in both FFPE and frozen tumor tissues of GC.

• Journal of Gastric Cancer
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• v.4 no.2
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• pp.82-88
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• 2004

Purpose: E-cadherin and CD44H have been shown to play a role in the progression and the metastasis of tumors. This study evaluated the clinical correlations between expression of E-cadherin and CD44H and various clinicopathologic factors and the value of expressions of E-cadherin and CD44H as prognostic factors in Borrmann type IV gastric cancer. Materials and Methods: In 122 patients with Borrmann type IV gastric cancer, we performed the immunohistochemical stainings for E-cadherin and CD44H. We analyzed the correlation between the expressions of E-cadherin and CD44H and lymphatic invasion, venous invasion, perineural invasion, histologic type, lymph node metastasis, depth of invasion, stage, and peritoneal dissemination, and survival. Results: There were no correlations between reduced expression of E-cadherin and CD44H and lymphatic invasion, venous invasion, perineural invasion, histologic type, lymph node metastasis, depth of invasion, and stage. However, there was a significant correlation between lymph node metastasis and the lymphatic invasion (P=0.022). There was also a significant correlation between the peritoneal dissemination and CD44H expression (P=0.005). The 5-year survival rate was correlated with CD44H expression expression (P=0.026), peritoneal dissemination (P<0.01), depth of invasion (P<0.01), lymph node metastasis (P<0.01), stage of tumor (P<0.01), and lymphatic invasion (P<0.01). There was no correlation between expression of E-cadherin and survival rate. Conclusion: The expression of CD44H and peritoneal dissemination was correlated. The expression of CD44H was an independent prognostic factor in Borrmann type IV gastric cancer. Further prospective studies with a large number of cases are required.

• Journal of Gastric Cancer
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• v.1 no.3
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• pp.168-173
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• 2001

Purpose: A positive esophageal margin is encountered in a total gastrectomy not infrequently. The aim of this retrospective review was to evaluate whether a positive esophageal margin predisposes a patient to loco-regional recurrence and whether it has an independent impact on long-term survival. Materials and Methods: A retrospective review of 224 total gastrectomies for adenocarcinomas was undertaken. The Chisquare test was used to determine the statistical significance of differences, and the Kaplan-Meier method was used to calculate survival rates. Significant differences in the survival rates were assessed using the log-rank test, and independent prognostic significance was evaluated using the Cox regression method. Results: The prevalence of esophageal margin involvement was $3.6\%$ (8/224). Univariate analysis showed that advanced stage (stage III/IV), tumor size ($\geq$5 cm), tumor site (whole or upper one-third of the stomach), macroscopic type (Borrmann type 4), esophageal invasion, esophageal margin involvement, lymphatic invasion, and venous invasion affected survival. Multivariate analysis demonstrated that TNM stage, venous invasion, and esophageal margin involvement were the only significant factors influencing the prognosis. All patients with a positive esophageal margin died with metastasis before local recurrence became a problem. A macroscopic proximal distance of more than 6 cm of esophagus was needed to be free of tumors, excluding one exceptional case which involved 15 cm of esophagus. Conclusion: All of the patients with a positive proximal resection margin after a total gastrectomy had advanced disease with a poor prognosis, but they were not predisposed to anastomotic recurrence. Early detection and extended, but reasonable, surgical resection of curable lesions are mandatory to improve the prognosis.

• Journal of Gastric Cancer
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• v.16 no.4
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• pp.215-220
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• 2016

Purpose: This study aimed to evaluate the rate, patterns, and risk factors associated with tumor recurrence in patients with T1N0 gastric cancer. Materials and Methods: The medical records of 8,753 patients with pathological T1N0M0 gastric cancer who underwent gastrectomy between 1994 and 2014 at Sungkyunkwan University School of Medicine were examined. Results: Among the 8,753 patients, 95 patients (1.1%) experienced tumor recurrence; this included 31 remnant, 27 hematogenous, 9 lymph nodal, 5 peritoneal, and 23 multiple-site recurrences. When patients were divided into two groups according to the presence of tumor recurrence, the following characteristics were higher in the recurrence group than in the non-recurrence group: older age (${\geq}65years$), male gender, undifferentiated histology, submucosal invasion, and venous invasion. In multivariate analysis, older age, male gender, tumor depth (sm2 and sm3 invasion), and venous invasion were independent risk factors for tumor recurrence. The recurrence rates were 0.7% in patients with less than two risk factors, 1.7% in those with two risk factors, 3.0% in those with three risk factors, and 6.3% in those with four risk factors (P<0.001). Conclusions: Although tumor recurrence is rare in pT1N0M0 gastric cancer, some patients with certain risk factors demonstrate an increased rate of tumor recurrence. Careful follow-up is required for patients with three or four risk factors.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.255-262
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• 2006

$\underline{Purpose}$: To evaluate the pathological prognostic factors related to local recurrence after radical surgery and adjuvant radiation therapy in advanced rectal cancer. $\underline{Materials\;and\;Methods}$: Fifty-four patients with advanced rectal cancer who were treated with radical surgery followed by adjuvant radiotherapy and chemotherapy between February 1993 and December 2001 were enrolled in this study. Among these patients, 14 patients experienced local recurrence. Tissue specimens of the patients were obtained to determine pathologic parameters such as histological grade, depth of invasion, venous invasion, lymphatic invasion, neural invasion and immunohistopathological analysis for expression of p53, Ki-67, c-erb, ezrin, c-met, phosphorylated S6 kinase, S100A4, and HIF-1 alpha. The correlation of these parameters with the tumor response to radiotherapy was statistically analyzed using the chi-square test, multivariate analysis, and the hierarchical clustering method. $\underline{Results}$: In univariate analysis, the histological tumor grade, venous invasion, invasion depth of the tumor and the over expression of c-met and HIF-1 alpha were accompanied with radioresistance that was found to be statistically significant. In multivariate analysis, venous invasion, invasion depth of tumor and over expression of c-met were also accompanied with radioresistance that was found to be statistically significant. By analysis with hierarchical clustering, the invasion depth of the tumor, and the over expression of c-met and HIF-1 alpha were factors found to be related to local recurrence. Whereas 71.4% of patients with local recurrence had 2 or more these factors, only 27.5% of patients without local recurrence had 2 or more of these factors. $\underline{Conclusion}$: In advanced rectal cancer patients treated by radical surgery and adjuvant chemo-radiation therapy, the poor prognostic factors found to be related to local recurrence were HIF-1 alpha positive, c-met positive, and an invasion depth more than 5.5 mm. A prospective study is necessary to confirm whether these factors would be useful clinical parameters to measure and predict a radio-resistance group of patients.

• Journal of Gastric Cancer
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• v.9 no.4
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• pp.193-199
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• 2009

Purpose: The aim of this study was to evaluate the clinicopathologic features, treatment outcomes, and prognostic factors of gastric cancer based on 14 years' experience in a single medical center, and to compare treatment outcomes with a previous study. Materials and Methods: We retrospectively studied 2,327 patients who were operated on for gastric cancer between 1993 and 2006 at Korea University Hospital. Results: The resection rate was 92.8% and curative resection was achieved for 1,960 (90.8%) patients. The 5-year survival rate was 70.0% for all patients undergoing resection and 79.2% for patients undergoing curative resection. The 5-year survival rate was 1.5% for unresected cases. Age, tumor size, location of the tumor, gross tumor type, depth of tumor invasion, lymph node involvement, distant metastasis, tumor stage, combined resection, complications, histology, and type of operation each had prognostic significance on univariate analysis. On multivariate analysis, lymph node involvement, depth of invasion, venous invasion, and age were independent prognostic factors. Conclusion: The 5-year survival rate for patients who underwent curative resection was 79.2%. Depth of invasion, lymph node involvement, venous invasion, and age were independent prognostic factors. The fact that tumor stage is the most important prognostic factor after curative resection, increases the importance of early detection.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3149-3152
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• 2012

Objective: The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated but not clearly clarified. The objective of our study was to investigate the role of PNI as prognostic factor in patients undergoing curative surgical resection and without distant metastasis in comparison with other clinicopathological factors. Methods: Between 2001 and 2010, 287 cases of gastric adenocarcinoma underwent radical gastrectomy recorded in hospital based registries. PNI was assessed as positive when cancer cells were seen in the perinerium or neural fascicles intramurally. Categorical and continuous variables were summarized using descriptive statistics and compared using chi-square and Mann-Whitney U tests, respectively. Cancer related survival rates were estimated by the Kaplan-Meier method. Results: PNI was positive in 211 of 287 cancers (73%), with a positive relation to lymph node metastases and advanced stage (p=0.0001, p=0.0001, respectively), mural invasion, and lymphatic and blood vessel invasion (p=0.0001, p=0.0001, respectively). The median survival of the PNI positive patients was significantly shorter than that of their PNI negative counterparts (24.1 versus 38.2 months, p=0.008). In the multivariate analysis, we detected PNI was an independent prognostic factor (p=0.025, HR=1.21, 95% CL 1.08-2.3) along with classical clinicopathological variables such as lymph node involvement (p=0.001), pT stage (p=0.03), and LVI (p=0.017), but not age, gender, tumour localization, stage, histologic type, and surgery procedure. Conclusions: PNI positivity in gastric cancers was related mural invasion, lymph node involvement, advanced stage and lymphatic and venous blood vessels. The presence of PNI appeared as an independent prognostic factor on survival on multivariate analysis, not influenced by tumor stage, lymph node metastases and other classical factors.