• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6447-6453
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• 2012

Background: The mucin components of the gastric gel layer function as a protective and lubricating factor against luminal acid and proteolytic enzymes. Alteration of mucin expression in gastric preneoplastic and neoplastic lesions has suggested potential roles in neoplastic processes. This study aimed to assess the clinicopathological and prognostic significance of MUC-2, MUC-4 and MUC-5AC in Japanese gastric cancer. Methods: Expression of MUC-2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas and adjacent non-cancerous mucosa specimens by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients. Results: The three mucins were found to be expressed to a lesser extent in gastric carcinomas in comparison with non-cancerous mucosa (p<0.05). MUC-2 expression was negatively correlated with tumor size, depth of invasion, and TNM staging of gastric cancer (p<0.05), while that of MUC-5AC was negatively associated with the depth of invasion, venous invasion, lymph node metastasis and TNM staging (p<0.05), but positively with MUC-4 and MUC-2 expression (p<0.05). There was higher MUC-2 expression in intestinal- than diffuse-type carcinomas (p<0.05). Kaplan-Meier analysis indicated no relationship between expression of the three mucins and the cumulative survival rate of patients, even stratified according to the depth of invasion (p>0.05). Conclusion: Down-regulated expression of MUC-2, -4 and -5AC may be involved in pathogenesis, invasion, metastasis or differentiation of gastric carcinoma. Their altered expression might therefore be employed as an indicator of pathobiological behavior.

• 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.

• Journal of Gastric Cancer
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• v.6 no.2
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• pp.84-90
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• 2006

Purpose: The macroscopic findings of tumors are not always identical with the microscopic findings. This study investigated the oncologic implications of macroscopic serosal invasion in advanced gastric cancer to find out how to improve the accuracy for the depth of invasion assessed by the surgeon during an operation. Materials and Methods: The medical records of 789 patients with advanced gastric cancer who underwent a gastrectomy at Kyungpook National University Hospital between 1995 and 1999 were reviewed. The prognoses and the recurrence patterns were analyzed according to macroscopic serosal invasion and microscopic serosal invasion, and the clinico-pathological factors of cT3/ss cancers were compared with those of cT3/se cancers. Results: Difference of survival rates according to macroscopic serosal invasion and microscopic serosal invasion revealed statistically significant. Recurrence rates were similar in patients with macroscopic and microscopic serosal invasion (42.2% and 41.4%, respectively). Peritoneal recurrence rates were also similar (19.8% and 21.9%, respectively). The sensitivity and the specificity of macroscopic assessment of serosal invasion were 70.3% and 77.8%, respectively, On univariate and multivariate analyses, Borrmann type I/II cancers and the absence of distant metastases revealed the risk factors for overestimating of serosal invasion. Conclusion: Macroscopic serosal invasion assessed by a surgeon intraoperatively can be used to give a prognosis and to predict the recurrence pattern precisely, although there is a risk for overestimation when the tumor is a Borrmann type I/II cancer or the tumor has no distant metastases. (J Korean Gastric Cancer Assoc 2006;6:84-90)

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.519-522
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• 2015

Background: We aimed to investigate whether the tumor free distance (the distance between the uterine serosa and the tumor at its deepest point) is useful in surgical staging and in predicting prognosis. Materials and Methods: Data from patients who underwent complete surgical staging for endometrial cancer between January 2006 and June 2011 were reviewed retrospectively. All demographic findings, surgical stages, histological type and grade, myometrial invasion, lymphovascular space invasion as well as abdominal cytology, cervical, adnexal, and omental involvement, and lymph node metastasis were recorded. The relations between myometrial invasion and tumor free distance from uterine serosa with prognostic factors were investigated. Results: Seventy patients were included in the study. Sixty-four (91.5%) had endometrioid type cancers and forty-four (62.9%) were grade 1. The deepest myometrial invasion was less than 1/2 in 42 patients (60%). In 18 patients (25.8%) lymphovascular invasion was noted. Eight (11.4%) were found to have cervical involvement, five (7.1%) had adnexal involvement and in 4 cases (5.7%) the peritoneal washings included malignant cells. Four patients had pelvic and one para-aortic node metastasis. We recognized that an invasion of more than 1/2 was correlated significantly with lymphovascular space involvement, histological grade, positive abdominal washing cytology, nodal and cervical involvement, but not with adnexal involvement. Tumor-free myometrial thickness was negative and statistically significant correlated with surgical stage, histological grade, lymphovascular space involvement, positive abdominal washing cytology, cervical and adnexal involvement. The importance of tumor-free myometrial thickness in determinating the lymphovascular space invasion was found to be highest in terms of sensitivity and specificity when crossing the ROC curve at 11 millimeters. Conclusions: Depth of myometrial invasion is more valuable for predicting lymph node metastasis than tumor-free myometrial thickness. The tumor-free myometrial thickness provides a better prediction for adnexal involvement.

• Journal of Gastric Cancer
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• v.12 no.3
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• pp.149-155
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• 2012

Purpose: Although serosal invasion is a critical predisposing factor for peritoneal dissemination in advanced gastric cancer, the accuracy of preoperative assessment using routine imaging studies is unsatisfactory. This study was conducted to identify high-risk group for serosal invasion using preoperative factors in patients with advanced gastric cancer. Materials and Methods: We retrospectively analyzed clinicopathological features of 3,529 advanced gastric cancer patients with Borrmann type I/II/III who underwent gastrectomy at Korea Cancer Center Hospital between 1991 and 2005. We stratified patients into low-(${\leq}40%$), intermediate-(40~70%), and high-risk (>70%) groups, according to the probability of serosal invasion. Results: Borrmann type, size, longitudinal and circumferential location, and histology of tumors were independent risk factors for serosal invasion. Most tumors of whole stomach location or encircling type had serosal invasion, so they belonged to high-risk group. Patients were subdivided into 12 subgroups in combination of Borrmann type, size, and histology. A subgroup with Borrmann type II, large size (${\geq}7$ cm), and undifferentiated histology and 2 subgroups with Borrmann type III, large size, and regardless of histology belonged to high-risk group and corresponded to 25% of eligible patients. Conclusions: This study have documented high-risk group for serosal invasion using preoperative predictors. And risk stratification for serosal invasion through the combination with imaging studies may collaboratively improve the accuracy of preoperative assessment, reduce the number of eligible patients for further staging laparoscopy, and optimize therapeutic strategy for each individual patient prior to surgery.

• Journal of Gastric Cancer
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• v.14 no.2
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• pp.111-116
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• 2014

Purpose: The standard surgical procedure recommended to treat gastric cancer in advanced cases is dissection of D2 lymph nodes (LNs). However, the optimum number of LNs that should be retrieved in advanced gastric cancer (AGC) remains debatable. Therefore, this study aimed to investigate the optimum number of retrieved LNs and determine the clinical implications of retrieved LN numbers on the treatment of AGC. Materials and Methods: Of 575 AGC patients reviewed, 369 who underwent open curative gastrectomy with D2 or more extensive LN dissection at our institution were analyzed according to their clinicopathologic characteristics and number of LNs retrieved. Results: Multivariate regression analysis revealed that tumor size (P=0.006), depth of invasion (P=0.000), LN metastasis (P=0.000), and stage (P=0.000) were independent variables with predictive value. The 5-year survival rates were differed significantly according to the numbers of LNs retrieved ([1] 15~25 vs. >25 and [2] 15~39 vs. ${\geq}40$) in patients with differentiated carcinoma. Conclusions: Tumor size, depth of invasion, LN metastasis, and stage were independent predictive factors for survival. The number of retrieved LNs was significantly associated with a long-term survival benefit in patients with differentiated carcinoma. Therefore, our data suggest that the retrieval of a minimum of 15 LNs may not be sufficient to warrant a recommendation for further curative surgery and that extensive LN dissection should be considered in advanced carcinoma of the differentiated type.

• Journal of Gastric Cancer
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• v.1 no.4
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• pp.197-201
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• 2001

Purpose: There are variants of gastric cancer assoclated with predominantly peritoneal spread of with haematogenous metastases. Perioperative intraperitoneal chemotherapy as an adjuvant to surgery is considered as a rational therapeutic modality to prevent peritoneal spread. We evaluated the influence of early postoperative intraperitoneal chemotherapy on the prognosis of resectable advanced gastric cancer. Materials and Methods: From 1990 to 1995, 246 patients with biopsy proven advanced gastric cancer were enrolled in the study. Among them 123 patients received early postoperative intraperitoneal mitomycin C and 5-fluorouracil. The survival rate was calculated using by the Kaplan-Meier method and was compared using the log-rank test according to 13 clinico-pathologic factors. Multivariate analysis was performed with the Coxproportional hazards model. Results: Gastric resection plusearly postoperative intraperitoneal chemotherapy showed an improved survival rate as compared to surgery alone ($54.1\%\;versus\;40.3\%;$ P=0.0325). Depth of tumor invasion, degree of regional lymph vode metastasis, distant metastasis, tumor size, tumor location, extent of gastric resection, and curability of surgery significantly influenced survival. When a multivariate analysis was performed, depth of tumor invasion, lymph node metastasis, early postoperative intraperitoneal chemotherapy, curability of surgery, and extent of gastric resection emerged as the statistically significant and independent prognostic factors. Conlusion: Early postoperative intraperitoneal chemotherapy is one of the independent prognostic indicators of resectable advanced gastric cancer.

• Clinical Endoscopy
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• v.51 no.6
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• pp.527-533
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• 2018

There have been many advances in endoscopic imaging technologies. Magnifying endoscopy with narrow-band imaging is an innovative optical technology that enables the precise discrimination of structural changes on the mucosal surface. Several studies have demonstrated its usefulness and superiority for tumor detection and differential diagnosis in the stomach as compared with conventional endoscopy. Furthermore, magnifying endoscopy with narrow-band imaging has the potential to predict the invasion depth and tumor margins during gastric endoscopic submucosal dissection. Classifications of the findings of magnifying endoscopy with narrow-band imaging based on microvascular and pit patterns have been proposed and have shown excellent correlations with invasion depth confirmed by microscopy. In terms of tumor margin prediction, magnifying endoscopy with narrow-band imaging offers superior delineation of gastric tumor margins compared with traditional chromoendoscopy with indigo carmine. The limitations of narrow-band imaging, such as the need for considerable training, long procedure time, and lack of studies about its usefulness in undifferentiated cancer, should be resolved to confirm its value as a complementary method to endoscopic submucosal dissection. However, the role of magnifying endoscopy with narrow-band imaging is expected to increase steadily with the increasing use of endoscopic submucosal dissection for the treatment of gastric tumors.

• Journal of Gastric Cancer
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• v.1 no.1
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• pp.10-16
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• 2001

Purpose: The p53 protein is a tumor supressor gene, and its mutation is associated with biologic aggressiveness. CD44v6, one of the CD44 family, is a cell surface glycoprotein that plays a role in cancer invasion and metastasis. Vascular endothelial growth factor (VEGF) is another recently identified growth factor with significant angiogenic properties. The purpose of this study was to investigate p53, CD44v6, and VEGF expressions to determine whether degree of expression was related to pathological parameters such as Lauren's classification, depth of invasion, and lymph node metastasis. Materials and Methods: Immunohistochemical stains of p53, CD44v6, and VEGF in formalin-fixed paraffin-embedded tissue sections of 125 gastric adenocarcinomas were done. Results: The overall expression rates of p53, CD44v6, and VEGF were $54.4\%$ (68/125), $36.8\%$ (46/125), and $48.0\%$ (60/125), respectively. The p53, not CD44v6 and VEGF was higher in intestinal-type gastric carcinomas by Lauren's classification. The expressions of p53, CD44v6, and VEGF were statistically correlated with depth of tumor invasion. The expression of CD44v6 was higher in the lymph node metastatic group than in the negative group. The p53 expression was significantly associated with VEGF expression. Conclusions: These data suggest that the expressions of p53, CD44v6, and VEGF are biologically related to malignancy. The p53 and CD44v6 expressions are independent; however, p53 gene mutation is one of the contributing factors to VEGF expression in gastric adenocarcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1489-1492
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• 2016

Background: Although there are no biomarkers that are routinely used in endometrial cancer (EC) management, many studies have found that serum human epididymis protein 4 (HE4) is superior to cancer antigen 125 (CA125) in the detection of EC. The correlation of HE4 with two prognostic factors for EC, primary tumor diameter (PTD) and depth of myometrial invasion (DMI) may be useful in identifying EC patients at high risk of lymphatic dissemination. Objective: To evaluate the correlation of serum HE4 with PTD and DMI in patients with EC. Materials and Methods: A cross-sectional study was conducted on 70 EC patients who were scheduled for elective surgery at Rajavithi Hospital between 1st September 2013 and 30th May 2014. Preoperative serum levels of HE4 and CA125 were investigated, and then gross measurement of PTD was taken and postoperative pathologic slides were reviewed for DMI including histologic types, grading and staging. Results: Preoperative serum HE4 levels were strongly correlated with PTD (r=0.65, p<0.001) and moderately correlated with DMI (r=0.46, p<0.001). Moreover, serum HE4 levels were significantly elevated in EC patients with PTD >2 cm (p<0.001) and DMI > 50% (p=0.004). The performance of serum HE4 in identifying EC patients at low risk and high risk of lymph node metastasis was significantly better than that of CA125 (AUC 0.88 vs. 0.65, p=0.003). At an optimal cut-off value of 70 pM/L, serum HE4 had a sensitivity of 83.3% and a specificity of 80.0%. Conclusions: In EC patients, preoperative serum HE4 is significantly correlated with PTD and DMI. Serum HE4 levels could be useful in identifying endometrial cancer patients at high risk of lymphatic spread who would benefit from systemic lymphadenectomy at the cut-off value of 70 pM/L.