• Journal of Gastric Cancer
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• v.11 no.3
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• pp.162-166
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• 2011

Purpose: Endoscopic resection is widely accepted as standard treatment for early gastric cancer (EGC) without lymph node metastasis. The procedure is minimally invasive, safe, and convenient. However, surgery is sometimes needed after endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD) due to perforation, bleeding, or incomplete resection. We evaluated the role of surgery after incomplete resection. Materials and Methods: We retrospectively studied 29 patients with gastric cancer who underwent a gastrectomy after incomplete EMR/ESD from 2006 to 2010 at Korea University Hospital. Results: There were 13 incomplete resection cases, seven bleeding cases, three metachronous lesion cases, three recurrence cases, two perforation cases, and one lymphatic invasion case. Among the incomplete resection cases, a positive vertical margin was found in 10, a positive lateral margin in two, and a positive vertical and lateral margin in one case. Most cases (9/13) were diagnosed as mucosal tumors by endoscopic ultrasonography, but only three cases were confirmed as mucosal tumors on final pathology. The positive residual tumor rate was two of 13. The lymph node metastasis rate was three of 13. All lymph node metastasis cases were submucosal tumors with positive lymphatic invasion and no residual tumor in the gastrectomy specimen. No cases of recurrence were observed after curative resection. Conclusions: A gastrectomy is required for patients with incomplete resection following EMR/ESD due to the risk of residual tumor and lymph node metastasis.

• Journal of Gastric Cancer
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• v.20 no.4
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• pp.442-453
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• 2020

Purpose: Expanded indications for endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) remain controversial due to the potential risk of undertreatment after adequate lymph node dissection (LND). Regional LND (RLND) is a novel technique used for limited lymphadenectomy to avoid gastrectomy. This study established the safety and effectiveness of RNLD as an additional treatment option after ESD for expanded indications. Materials and Methods: A total of 69 patients who met the expanded indications for ESD were prospectively enrolled from 2014 to 2017. The tumors were localized using intraoperative esophagogastroduodenoscopy (EGD) before RLND. All patients underwent RLND first, followed by conventional radical gastrectomy with LND. The locations of the preoperative and intraoperative EGD were compared. Pathologic findings of the primary lesion and the RLND status were analyzed. Results: The concordance rates of tumor location between the preoperative and intraoperative EGD were 79.7%, 76.8%, and 63.8% according to the longitudinal, circumferential, and regional locations, respectively. Of the 4 patients (5.7%) with metastatic LNs, 3 were pathologically classified as beyond the expanded indication for ESD and 1 had a single LN metastasis in the regional lymph node. Conclusions: RLND is a safe additional option for the treatment of EGC in patients meeting expanded indications after ESD.

• Journal of Gastric Cancer
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• v.9 no.3
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• pp.96-103
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• 2009

Purpose: Lymph node metastasis is an important factor in determining prognosis and therapeutic options for early gastric cancer (EGC) patients. Vascular endothelial growth factor (VEGF)-C and D are known as lymphangiogenic factors, and cyclooxygenase (COX)-2 is thought to play a role in lymph node metastasis in gastric carcinoma. This study was designed to determine whether the expression of VEGF-C, VEGF-D, and COX-2 is associated with clinicopathologic factors, especially lymph node metastasis in EGCs invading the submucosa. Materials and Methods: Tissue samples were obtained from 85 Patients undergoing standard gastrectomy with lymph node dissection between 1991 and 2007 in the Department of Surgery of Daejeon St. Mary's Hospital in Daejeon, Korea. All patients were diagnosed with gastric cancers and submucosal invasion. We examined the expression of VEGF-C, VEGF-D, and COX-2 using immunohistochemical methods. Results: Of the 85 patients, 16 (18.8%) had lymph node metastasis. VEGF-C, VEGF-D, and COX-2 were positively expressed in 34.1% (29/85), 22.3% (19/85), and 37.6% (32/85) of the patients. VEGF-C and COX-2 expression was significantly correlated with lymph node metastasis (P<0.05). A positive correlation existed between VEGF-C and COX-2 expression (P< 0.001). Conclusion: VEGF-C and COX-2 expression is associated with lymph node metastasis in gastric cancer with submucosal invasion. VEGF-C and COX-2 may thus be predictive markers for lymph node metastasis in EGC patients with submucosal invasion.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.1.1-1.14
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• 2018

DNA methylation is a regulatory mechanism in epigenetics that is frequently altered during human carcinogenesis. To detect critical methylation events associated with gastric cancer (GC), we compared three DNA methylomes from gastric mucosa (GM), intestinal metaplasia (IM), and gastric tumor (GT) cells that were microscopically dissected from an intestinal-type early gastric cancer (EGC) using methylated DNA binding domain sequencing (MBD-seq) and reduced representation bisulfite sequencing (RRBS) analysis. In this study, we focused on differentially methylated promoters (DMPs) that could be directly associated with gene expression. We detected 2,761 and 677 DMPs between the GT and GM by MBD-seq and RRBS, respectively, and for a total of 3,035 DMPs. Then, 514 (17%) of all DMPs were detected in the IM genome, which is a precancer of GC, supporting that some DMPs might represent an early event in gastric carcinogenesis. A pathway analysis of all DMPs demonstrated that 59 G protein-coupled receptor (GPCR) genes linked to the hypermethylated DMPs were significantly enriched in a neuroactive ligand-receptor interaction pathway. Furthermore, among the 59 GPCRs, six GI hormone receptor genes (NPY1R, PPYR1, PTGDR, PTGER2, PTGER3, and SSTR2) that play an inhibitory role in the secretion of gastrin or gastric acid were selected and validated as potential biomarkers for the diagnosis or prognosis of GC patients in two cohorts. These data suggest that the loss of function of gastrointestinal (GI) hormone receptors by promoter methylation may lead to gastric carcinogenesis because gastrin and gastric acid have been known to play a role in cell differentiation and carcinogenesis in the GI tract.

• Journal of Gastric Cancer
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• v.5 no.2
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• pp.101-105
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• 2005

Purpose: Some gastric cancer patients in whom the cancer has infiltrated up to the muscularis propria (mp) have a good postoperative course similar to that of early gastric cancer (EGC) patients (this does not match the general classification of gastric cancer). Therefore, we performed a retrospective analysis of 125 patients with mp gastric cancer based on the degree of mp invasion. Materials and Methods: The clinicopathologic features of 125 cases of mp gastric cancer were subdivided according to depth of invasion, and were retrospectively reviewed and compared with the surgical features of 222 patients with gastric cancer invading the submucosa (sm). For each tumor, using the section that showed the greatest extent of invasion, we evaluated the degree of tumor invasion into the mp layer at a magnification of $\times$100. The patients were classified into 2 groups: mp1, the tumor was limited to the first of the 3 mp layers, and mp2, the tumor had expanded beyond the first layer. Results: Patients with mp1 (n=50) had a significantly lower incidence of lymph node metastasis, and a smaller tumor size than patients with mp2 (n=75) (P=0.01 and P=0.029, respectively). The 5-year survival rate of mp1 patients was significantly better than that of mp2 patients ($95.3\%\;vs.\;77.6\%$, P=0.0282), but was similar to that ($91.2\%$) of the 222 sm patients. The 5-year survival rate of mp patients without lymph node metastasis (n=55) was significantly better than that of those with lymph node metastasis (n=70)($93.3\%\;vs.\;78.2\%$, P=0.0192). Patients with mp1 had a significantly higher incidence of lymph node metastasis ($42.5\%\;vs\;23\%$, P=0.006) than patients with sm. Conclusion: There were clear differences in clinical features between the mp1 and the mp2 patients. Subdivision of mp gastric cancer according to the depth of invasion may enable a more precise prognosis and a more pertinent treatment plan for mp patients. In particular, as the clinicopathological findings and surgical outcomes for mp1 patients were akin to those of the sm patients, mp1 patients may require treatment analogous to that administered to patients with sm gastric cancer. (J Korean Gastric Cancer Assoc 2005;5:101-105)

• Journal of Gastric Cancer
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• v.8 no.1
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• pp.20-26
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• 2008

Purpose: Pylorus-preserving gastrectomy (PPG), which retains pyloric ring and gastric function, has been accepted as a function-preserving procedure for early gastric cancer for the prevention of postgastrectomy syndrome. This study was compared laparoscopy-assisted pylorus-preerving gastrectomy (LAPPG) with laparoscopy-assisted distal gastrectomy with Billroth-I reconstruction (LADGB I). Materials and Methods: Between November 2006 and September 2007, 39 patients with early gastric cancer underwent laparoscopy-assisted gastrectomy in the Department of Surgery at Korea Cancer Center Hospital. 9 of these patients underwent LAPPG and 18 underwent LADGBI. When LAPPG was underwent, we preserved the pyloric branch, hepatic branch, and celiac branch of the vagus nerve, the infrapyloric artery, and the right gastric artery and performed D1+$\beta$ lymphadenectomy to the exclusion of suprapyloric lymph node dissection. The distal stomach was resected while retaining a $2.5{\sim}3.0\;cm$ pyloric cuff and maintaining a $3.0{\sim}4.0\;cm$ distal margin for the resection. Results: The mean age for patients who underwent LAPPG and LADGBI were $59.9{\pm}9.4$ year-old and $64.1{\pm}10.0$ year-old, respectively. The sex ratio was 1.3 : 1.0 (male 5, female 4) in the LAPPG group and 2.6 : 1.0 (male 13, female 5) in the LADGBI group. Mean total number of dissected lymph nodes ($28.3{\pm}11.9$ versus $28.1{\pm}8.9$), operation time ($269.0{\pm}34.4$ versus $236.3{\pm}39.6$ minutes), estimated blood loss ($191.1{\pm}85.7$ versus $218.3{\pm}150.6\;ml$), time to first flatus ($3.6{\pm}0.9$ versus $3.5{\pm}0.8$ days), time to start of diet ($5.1{\pm}0.9$ versus $5.1{\pm}1.7$ days), and postoperative hospital stay ($10.1{\pm}4.0$ versus $9.2{\pm}3.0$ days) were not found significant differences (P>0.05). The postoperative complications were 1 patient with gastric stasis and 1 patient with wound seroma in LAPPG group and 1 patient with left lateral segment infarct of liver in the LADGB I group. Conclusion: Patients treated by LAPPG showed a comparable quality of surgical operation compared with those treated by LADGBI. LAPPG has an important role in the surgical management of early gastric cancer in terms of quality of postoperative life. Randomized controlled studies should be undertaken to analyze the optimal survival and long-term outcomes of this operative procedure.

• Journal of Gastric Cancer
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• v.1 no.2
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• pp.92-99
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• 2001

Purpose: E-cadherin is an adhesion molecule essential for tight connection between cells, forming the cadherin/catenin complex. Truncated $\beta$-catenin disrupts the interaction between E-cadherin and $\alpha$-catenin, leading to the loss of intercellular adhesion. Met protein, the hepatocyte growth factor receptor, plays important roles in signal transduction. We investigated the relationships between the expressions of E-cadherin, $\beta$-catenin, and c-met protein and the clinicopathological and prognostic parameters in gastric adenocarcinomas. Materials and Methods: The patterns of E-cadherin, $\beta$-catenin, and c-met protein expression were studied using immunohistochemistry in formalin-fixed, paraffin-embedded archival tissues from 76 surgically resected gastric adenocarcinomas. Results: Increased expressions of E-cadherin, $\beta$-catenin, and c-met were more significantly correlated in early gastric cancers (EGC) than in advanced gastric cancers (AGC) (P=0.002, P=0.003 and P=0.026). The positive immunoreactivities of all three markers were markedly lower in signet ring-cell type and poorly differentiated type lesions than in intestinal-type lesions. Decreased expression of the $\beta$-catenin protein correlated well with increased tumor invasion depth (P=0.039), and increased lymph node metastasis correlated well with reduced expression of c-met (P=0.046). Conclusion: In gastric cancers, reduced expressions of the E-cadherin, $\beta$-catenin, and c-met proteins may play some role in poorer tumor differentiation, deeper tumor invasion, and increased lymph node metastasis. Also, the c-met gene is thought to play a specific role in the mechanism of the yet unknown catenin action.

• Journal of Gastric Cancer
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• v.7 no.4
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• pp.206-212
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• 2007

Purpose: The number of laparoscopy assisted distal gastrectomies (LADG) is gradually increasing for the treatment of early gastric cancer (EGC) patients as a surgical modality for improving quality of life. However, there are few reports on laparoscopy-assisted total gastrectomy (LATG), mainly because this procedure is performed relatively infrequently, and the procedure is more complicated than LADG. This study was performed to evaluate the technical feasibility, safety, and surgical results of LATG with lymphadenectomy through a review of our experience. Materials and Methods: From July 2003 to June 2007, 77 LATG with Roux-en-Y esophagojejunostomy were performed for patients with a preoperative diagnosis of EGC. The clinicopathological features and surgical outcomes were analyzed. Results: There were 49 males and 28 females in the study with a mean age of 61 years (range $30{\sim}85$ years). The mean operation time was 210 minutes (range $100{\sim}400$ minutes) and the operation time was gradually decreased as the case numbers increased. There were 13 operative morbidities (16.9%) and no operative mortalities. The restoration of bowel motility was noted at 3.2 postoperative days; a soft diet was started at 4.4 postoperative days and the duration of hospital stay was 10 days. There were 20 mucosal lesions, 32 submucosal lesions, 15 proper muscle lesions, 7 subserosal lesions and 3 serosal lesions. A total of 20 patients were treated by D2 lymph node dissection, 55 patients were treated by D1+$\beta$ lymph node dissection, and two patients were treated by D1+$\alpha$ lymph node dissection. The mean number of retrieved lymph nodes was 42 (range $11{\sim}86$). Lymph node metastases were noted in 12 patients. Conclusion: This study indicated LATG could be applied safely and effectively for patients with EGC. However, a prospective study comparing laparoscopy-assisted versus open gastrectomy for short-term and long-term surgical outcome is needed.

• Journal of Gastric Cancer
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• v.8 no.4
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• pp.232-236
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• 2008

Purpose: Laparoscopic surgery for gastric cancer was introduced in the past decade because it was considered less invasive than open surgery, and this results in less postoperative pain, faster recovery and an improved quality of life. Several studies have demonstrated the safety and feasibility of this procedure. We examined the outcome of performing laparoscopic surgery for gastric cancer over the last two year. Materials and Methods: From April 2004 to December 2006, 329 patients with gastric adenocarcinoma underwent a laparoscopy-assisted distal gastrectomy with lymph node dissection. The data was retrospectively reviewed in terms of the clinicopathologic findings, the perioperative outcomes and the complications. Results: The total patient group was comprised 196 men (59.6%) and 133 women (40.4%). The mean BMI was 23.6 and the mean tumor size was 2.7 cm. The mean number of harvested lymph node was 22.7, and this was 18.6 before 30 cases and 23.1 after 30 cases, and the difference was significant (P=0.02). The mean operation time was 180.9 min, and this was than 287.9 min before 30 cases and 170.2 min after 30 cases. After 30 cases, there was a significant improvement of the operation time (P<0.01). The mean incision length after 30 cases was shorter than that before 30 cases (P<0.01). Postoperative complications occurred in 24 (7.3%) of 329 patients and there was no conversion to open surgery. Conclusion: Even though the LADG was accompanied by a difficult learning curve, we successfully performed 329 LADG procedures over the past 2 years and we believe that LADG is a safe, feasible operation for treating most early gastric cancers (EGC).