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Background EMR with circumferential mucosal incision facilitates en bloc resection, which is the most important predictor for complete resection in the treatment of intramucosal gastric neoplasm. The objective of the study was to evaluate the efficacy and the safety of EMR with circumferential mucosal incision in relation to the endoscopist's experience. Methods In this retrospective study, we analyzed the outcome of 80 EMR procedures performed by a single endoscopist at the National Cancer Center, Goyang, Korea. The EMR procedure with circumferential mucosal incision was performed with a conventional needle knife. We compared the en bloc resection rate, the complete resection rate, the duration of the procedure time, and the associated complications by quartiles. Results From the first to the last quartile, en bloc resection rates were 55%, 45%, 85%, and 85% (p = 0.006), and complete resection rates were 65%, 60%, 90%, and 85% (p = 0.039). The increase in the mean en bloc and complete resection rates between the first two quartiles and the second two quartiles was significant (p = 0.002 and p = 0.019, respectively). Three perforations (15%) were reported in the first quartile and only one (1.7%) in the remaining 3 quartiles (p = 0.046). The procedure time also decreased after the first 20 cases (p = 0.004). Conclusions For an experienced endoscopist, EMR with circumferential mucosal incision could be performed effectively and safely after the experience of 40 cases.

Aims To determine the most efficient injection method for a sentinel node (SN) biopsy in gastric cancer. Methods Gastric adenocarcinoma patients without serosal invasion and distant metastasis were prospectively enrolled in this study. Isosulfan blue was injected into the subserosa (SS) of the first set of 71 consecutive patients and an intraoperative endoscopic submucosal (SM) injection of the same dye was injected into the second set of 50 consecutive patients. After the biopsy of blue-stained SNs, a gastrectomy with a D2 lymphadenectomy was performed. All dissected lymph nodes were evaluated for metastasis. The results of the SN biopsies were compared between the SS and SM dye injection methods. Results Detection rate (0.92 vs 0.94), mean number of SNs (2.5 vs 2.9) and sensitivity (0.61 vs 0.46) of the SN biopsies were not significantly different between the SS and SM injection methods ( P >0.05). The operation time was significantly shorter in the SS than the SM injection method (159.7 vs 172.7 min, P =0.030). Conclusions Both injection methods were equally efficient in their roles for a SN biopsy in gastric cancer. However, the SS injection method was more preferable due to its easy technique and short operation time.

Although the importance of genetic susceptibility to inflammatory bowel disease (IBD) has been established by epidemiological studies, the genes involved remain poorly understood. The aim of this study was to assess the role of single nucleotide polymorphisms of tumor necrosis factor-alpha(TNF-alpha) and interleukin-10 (IL-10) genes in genetic susceptibility of IBD.Blood samples were obtained from 91 patients with ulcerative colitis (UC), 63 patients with Crohn's disease (CD), and 200 healthy controls (HC). DNA was extracted from blood leukocytes for IL-10 and TNF-alpha genotyping by single base extension reaction. Genotypes and allelic frequencies were compared between IBD patients and HC, and among subgroups of the patients.The frequency of -308A allele of TNF-alpha was significantly lower in CD patients than in HC (p=0.005). The frequency of -238A allele of TNF-alpha was significantly higher in CD patients with perianal lesion than those without perianal lesion. On the other hand, the frequency of -308A allele of TNF-alpha was significantly higher in ANCA-positive IBD patients than ANCA-negative IBD patients. There were no significant differences in allelic frequencies in the promoter region of IL-10 between IBD patients and HC.The TNF-alpha gene polymorphisms at positions -308 and -238 may have influences on the susceptibility to CD or the behavior of CD.

The aim of this study was to assess the clinical features and therapeutic responses of perianal lesions in Crohn's disease.We retrospectively reviewed medical records of 94 cases with perianal lesions among 231 cases registered as Crohn's disease in Seoul National University Hospital between January 1975 and June 2001. The cases were investigated after dividing into two different groups. One group included the cases registered between January 1975 and December 1996 and the other group between January 1997 and June 2001.The perianal lesions were observed in 41% of the cases. Perianal lesions were more frequent in colonic Crohn's disease after 1997, but not before 1996. Fistula was significantly prevalent, followed by abscess, fissure, and stricture. Perianal lesions preceded intestinal symptoms such as abdominal pain and diarrhea in 25% of the cases. The remission rate with non-specific conservative treatment (10%) was lower than that before 1996. The remission rate after specific treatment (77%) was higher than that after surgery (53%). In cases of specific treatment, cumulative relapse rates were 7% in 1 year and 39% in 5 years.Crohn's disease should be considered in young male patients who have the refractory perianal lesions. Perianal lesions should be managed initially with medical treatment.

Background: Metformin use has been associated with a decreased incidence and mortality of various cancers. Aim: The aim of this study was to evaluate the association between metformin use and gastric cancer. Methods: We randomy selected 100,000 type 2 diabetic patients from the 2004 Korean National Health Insurance claim database, and assessed gastric cancer incidence among 39,989 patients (aged 30-97 years) who were regularly treated with anti-diabetic drugs and followed-up from 2004 to 2010. In total, 26,690 patients had used metformin out of 32,978 diabetics who had not regularly used insulin (insulin non-users), and 5,855 patients had used metformin out of 7,011 regular insulin users. Results: Patients who used metformin showed a lower incidence of gastric cancer than those who did not use metformin, in insulin non-users (P=0.047, log-rank test). However, in patients on regular insulin, there was no difference of gastric cancer incidence according to metformin use. In insulin non-users, the adjusted hazard ratio (AHR) for metformin use was 0.73 (95% confidential interval [CI], 0.53-1.01) with borderline statistical significance (P=0.059). Duration of metformin use was associated with the reduction of gastric cancer risk (AHR, 0.88; 95% CI 0.81-0.96, P=0.003), especially in patients that used metformin for more than 3 years (AHR, 0.57; 95% CI, 0.37-0.87; P=0.009). Conclusion: Metformin use >3 years in type 2 diabetics who do not use insulin is associated with significantly reduced gastric cancer risk. Citation Format: Soo-Jeong Cho, Young-Il Kim, So Young Kim, Jong-Hyock Park, Il Ju Choi, You Jin Lee, Eun Kyung Lee, Myeong-Cherl Kook, Chan Gyoo Kim, Keun Won Ryu, Young-Woo Kim. Long-term metformin use reduces gastric cancer risk in type 2 diabetics without insulin treatment: a nationwide cohort study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2136. doi:10.1158/1538-7445.AM2014-2136

100,000 adults, hospital admissions approaching 400,000 annually, recurrence rates estimated at 20% and mortality approaching 10-14%. Although the early use of a risk stratification score in upper GI bleeding is recommended, existing risk scores are not widely used in clinical practice. The purpose of this study was to construct a simple bedside prediction tool that accurately identifies patients at increased risk for in-hospital mortality after NVUGIB without the need for endoscopic parameters. Methods: This was a retrospective study at a tertiary care referral center between January 2008 and November 2011. All patients O 18 years of age admitted with a diagnosis of acute NVUGIB were included. Rebleeding was defined as NVUGIB following index endoscopic therapy within 30 days of an initial bleed. Demographics, presentation, comorbidities, medications, serum and hemodynamic parameters were collected. Multivariable logistic regression analysis was performed to build a model for prediction of rebleeding. Accuracy to predict mortality was assessed by the area under the receiver operating characteristic (AUROC) curve. Results: A total of 251 patients underwent EGD for NVUGIB (mean age 64 13 years, 39% female, 74% Caucasian). The most common source of bleeding was peptic ulcer disease (42%). A total of 123 (49%) patients had a recurrent bleed after index endoscopy. The average time to an episode of rebleeding was 3.5 6.1 days. The majority of patients only had 1 episode of rebleeding (58%). Average length of ICU stay was 15 days. The in-hospital mortality rate was 18% for all NVUGIB. The 4 factors present on admission with the best discrimination for mortality risk were age, platelets, WBC and diastolic blood pressure as depicted in the nomogram in Figure 1. The model had a high predictive accuracy (AUCROC Z 0.76; Figure 2). Conclusions: Efforts to identify patients at highest risk for recurrent non-variceal upper GI bleeding mortality are of significant clinical utility. This simple, accurate risk score reliably predicts with 76% accuracy in-hospital mortality in patients with recurrent non-variceal upper gastrointestinal bleeding. Figure 1. Nomogram for prediction of ICU mortality. Figure 2. Receiver Operating Characteristics (ROC) plot for prediction of ICU mortality. AB298 GASTROINTESTINAL ENDOSCOPY Volume 79, No. 5S : 2014 Sa1677 Risk Scoring Systems in Predicting Intervention and Clinical Outcomes of Bleeding in Patients With Unresectable Gastric Cancer Young-IL. Kim*, IL Ju Choi, Soo-Jeong Cho, Jong Yeul Lee, Chan Gyoo Kim, MI–Jung Kim, Hark Kyun Kim, Young Iee Park Center for Gastric Cancer, National Cancer Center, Korea, Gyeonggi-do, Republic of Korea Background & Aims: Pre-endoscopic Rockall score (RS), full RS, and Glasgow-Blatchford bleeding Score (GBS) are increasingly used to stratify the risk in patients with upper gastrointestinal bleeding (UGIB). The aim of this study was to evaluate the efficacy of those bleeding risk scoring systems in patients with UGIB due to unresectable advanced gastric cancer (AGC). Methods: We reviewed retrospectively the medical records of patients presenting with UGIB due to unresectable AGC at the National Cancer Center, Korea from May 2001 to June 2012. Pre-endoscopic RS, full RS and GBS were calculated. The area under the receiver operating characteristicscurve (AUC) was used to assess the performance of these scores to predict the need for interventions and clinical outcomes. Results: During the study period, 355 patients who presented with UGIB from unresectable AGC received endoscopy. Of these, interventions were needed in 118 (33.2%). A total of 115 patients (32.4%) underwent endoscopic therapy, 2 (0.6%) required transarterial embolization and one (0.3%) underwent surgery as an initial treatment. Full RS was useful to predict the need for intervention (AUC 0.77, P! 0.001) and 7-day mortality after bleeding (AUC 0.67, PZ 0.024). However, pre-endoscopic RS, full RS and GBS were not useful for the prediction of rebleeding after initial hemostasis (AUC 0.49, 0.54 and 0.54, respectively), the need for admission more than 3 days (AUC 0.57, 0.64 and 0.62, respectively) and 30-day mortality (AUC 0.51, 0.53 and 0.59, respectively). Conclusions: Full RS might be useful in predicting the need for interventions and 7day mortality of patients presented with UGIB due to unresectable AGC. Sa1678 Prevalence of Heyde’s Syndrome: Does It Just Pertain to Aortic Stenosis? a Case-Control Study Karen Draper, Robert J. Huang, Lauren B. Gerson* Gastroenterology, California Pacific Medical Center, San Francisco, CA; Medicine, Stanford University, Stanford, CA Background: Heyde’s syndrome is described as the relationship between aortic stenosis (AS) and gastrointestinal angiodysplastic lesions (GIAD). While prior studies have examined the prevalence of AS in patients with GIAD-associated GIB, there is little data regarding whether this syndrome exists in patients with other cardiac valvular disorders. Our study aimed to determine the prevalence of Heyde’s syndrome in patients with AS compared to a control group of patients with mitral regurgitation by examining rates of iron deficiency anemia and GIAD-associated GIB in these two groups. Methods: We used an echocardiography database at a single large academic medical center to identify adult patients with severe AS and moderate or severe mitral regurgitation (MR). Patients were excluded if they had active malignancy, hematologic conditions, end-stage renal disease, inflammatory bowel disease, history of colectomy, cirrhosis, or if they had no available lab values within 2 years of the echocardiogram. Records from identified patients were then reviewed to assess for the presence of anemia, iron deficiency, and/or overt gastrointestinal bleeding (GIB). GIB was defined as melena, hematochezia, hematemesis, or guaiac positive stool. Values for hemoglobin (Hb), mean corpuscular volume (MCV), and iron panel results from within 2 years of echocardiography were collected. We searched the endoscopy database to determine which patients underwent subsequent endoscopic procedures and location of findings. Estimating that 10% of patients with AS would have GIAD compared to 3% of patients with MR (similar to population controls), the estimate sample size was 152 in each group, using an alpha of 95% and power of 80%. Results: Out of 514 patients who were screened, a total of 298 patients were included in the study (142 MR, 156 AS). Patients with MR were younger and more likely to have congestive heart failure, but otherwise had similar co-morbidities (Table 1). The rates of anemia and microcytic anemia were similar in both groups. The MR group was more likely to have been evaluated for iron deficiency, however rates of confirmed iron deficiency were similar in the two groups. Overall incidence of GIB was similar between the two groups (MR 7.7% vs. AS 8.3%); however, rates of proven GIAD (MR 0% vs. AS 1.3%) and occult GIB (MR 36% vs. AS 54%) appeared higher among patients with aortic stenosis, though again not reaching statistical significance (Table 2). Conclusions: While the prevalence of AS in patients with obscure or GIAD-associated GIB has been shown in previous studies to be relatively common, our study did not suggest that the incidence in AS was greater compared to a control group with MR. Whether MR itself could predispose to GIADassociated GIB is a topic for further research. Table 1 Characteristics of the Study Patients Characteristics Severe AS (N[156) Moderate-Severe MR (N[142) www.giejourn p value Male 93 (60%) 77 (54%) NS Age 79 13.5 66 17 !0.0001

Various gastrointestinal anastomotic breakdown has been reported to be closed by endoscopic clipping. However, no report has been issued on the control of duodenal stump leakage after Billroth II gastrectomy by endoscopic clipping. The authors describe successful endoscopic clipping in a case of duodenal stump leakage. J. Surg. Oncol. 2009;100:80–81. © 2009 Wiley-Liss, Inc.

Since the first transgastric natural orifice transluminal endoscopic surgery was described, various applications and modified procedures have been investigated. Transgastric natural orifice transluminal endoscopic surgery for periotoneoscopy, cholecystectomy, and appendectomy all seem viable in humans, but additional studies are required to demonstrate their benefits and roles in clinical practice. The submucosal tunneling method enhances the safety of peritoneal access and gastric closure and minimizes the risk of intraperitoneal leakage of gastric air and juice. Submucosal tunneling involves submucosal tumor resection and peroral endoscopic myotomy. Peroral endoscopic myotomy is a safe and effective treatment option for achalasia, and the most promising natural orifice transluminal endoscopic surgery procedure. Endoscopic full-thickness resection is a rapidly developing natural orifice transluminal endoscopic surgery procedure for the upper gastrointestinal tract and can be performed with a hybrid natural orifice transluminal endoscopic surgery technique (combining a laparoscopic approach) to overcome some limitations of pure natural orifice transluminal endoscopic surgery. Studies to identify the most appropriate role of endoscopic full-thickness resection are anticipated. In this article, I review the procedures of natural orifice transluminal endoscopic surgery associated with the upper gastrointestinal tract.

Correspondence to Chan Gyoo Kim, M.D., Ph.D. Center for Gastric Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Korea Tel: +82-31-920-1120, Fax: +82-31-920-2798, E-mail: glse@chol.com Copyrightc 2013 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 헬리코박터 파이로리 감염과 혈액학적 이상

Endoscopic forceps biopsy is essential before planning an endoscopic resection of upper gastrointestinal epithelial tumors. However, forceps biopsy is limited by its superficiality and frequency of sampling errors. Histologic discrepancies between endoscopic forceps biopsies and resected specimens are frequent. Factors associated with such histologic discrepancies are tumor size, macroscopic type, surface color, and the type of medical facility. Precise targeting of biopsies is recommended to achieve an accurate diagnosis, curative endoscopic resection, and a satisfactory oncologic outcome. Multiple deep forceps biopsies can induce mucosal ulceration in early gastric cancer. Endoscopic resection for early gastric cancer with ulcerative findings is associated with piecemeal resection, incomplete resection, and a risk for procedure-related complications such as bleeding and perforation. Such active ulcers caused by forceps biopsy and following submucosal fibrosis might also be mistaken as an indication for more aggressive procedures, such as gastrectomy with D2 lymph node dissection. Proton pump inhibitors might be prescribed to facilitate the healing of biopsy-induced ulcers if an active ulcer is predicted after deep biopsy. It is unknown which time interval from biopsy to endoscopic resection is appropriate for a safe procedure and a good oncologic outcome. Further investigations are needed to conclude the appropriate time interval.

4028 Background: We conducted a randomized phase II study to compare continuous vs. intermittent S-1 + oxaliplatin (SOX) after induction of 6 cycles of SOX in patients (pts) with metastatic gastric cancer (MGC). Methods: Pts >18 yrs with chemo-naive MGC, normal organ function, ECOG PS 0-2, and measurable or evaluable lesion(s) were initially given an induction treatment of 6 cycles of SOX (S-1 40 mg/m2 bid on D1-14 + oxaliplatin 130 mg/m2 on D1 q 3 wks). Pts with CR/PR or SD were randomized to continue SOX (arm A) until progression/intolerable toxicity or discontinue until progression when SOX was re-administered (arm B). The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), response rate, safety, quality of life, and biomarker correlative studies. Results: From July 2007 to Dec 2010, a total of 250 pts entered into the study. Median age was 53 yrs (range, 24-69); PS 0/1/2=13/219/18; M/F=162/88. Three pts did not receive treatment and 126 (50.4%) discontinued treatment before or at the completion of 6 cycles of SOX due to progression (45.6%), pt refusal (2.8%), or adverse events (2.0%). A total of 121 pts were randomized: 59 (48.8%) to arm A and 62 (51.2%) to arm B. Clinical characteristics were well balanced between arms. SOX continuation resulted in a significant reduction in the risk of progression (median PFS, 10.5 months for arm A vs. 7.2 months for arm B; HR=0.57, 95% CI 0.39-0.84, p=0.005). With a median follow-up of 34.0 months (range, 10.5-53.3 months), there was no significant difference in OS (median OS, 22.6 months for arm A vs. 22.7 months for arm B; HR, 0.79, 95% CI 0.51-1.25, p=0.31). Arm A had higher rates of grade 3/4 fatigue (28.8% vs. 8.1%, p=0.004) and neuropathy (25.4% vs. 8.1%, p=0.014) but other grade 3/4 hematologic (neutropenia, 35.6% vs. 32.3%; thrombocytopenia, 23.7% vs. 21.0%; anemia, 15.3% vs. 6.5%) or non-hematologic toxicity rates were not significantly different. Conclusions: Continuous chemotherapy with SOX after induction therapy improved PFS but not OS. Supported by NCC Grant 1010180 (S-1 and oxaliplatin was provided by JEIL Pharm. Co., Ltd. and sanofi-aventis Korea Co., Ltd., respectively).

Routine Follow-up Biopsies to Detect Local Recurrence After Complete Endoscopic Resection for Early Gastric Cancer May Be Unnecessary Jong Yeul Lee*, IL Ju Choi, Soo-Jeong Cho, Chan Gyoo Kim, Myeong-Cherl Kook, Jun Ho Lee, Keun Won Ryu, Young-Woo Kim Center for Gastric Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea Background and study aims: Local recurrence due to residual tumor may occur at the endoscopic resection (ER) site after ER for early gastric cancer (EGC). The aims of this study were to evaluate the predictive factors for local recurrence and suggest an appropriate follow-up biopsy strategy. Patients and methods: We retrospectively reviewed 396 EGCs from 372 consecutive patients who underwent ER between January 2002 and April 2008. Cumulative recurrence rate were determined by the Kaplan-Meier method and Cox proportional hazards analysis was used to determine the risk factors for local recurrence. Results: Local recurrence at ER site was found in 17 cases among 396 lesions during a median follow-up period of 48 months. The 5-year cumulative local recurrence rate was 4.8%. Multivariate analyses determined that tumor involvement at the lateral resection margin [hazard ratio (HR): 35.9; P 0.001], an uncheckable lateral resection margin [HR: 16.8; P 0.001], an uncheckable or involved deep resection margin [HR: 3.76; P 0.047], and a piecemeal resection [HR: 3.95; P 0.007] were associated with local recurrence. If a lesion was positive for any of these risk factors, the 5-year cumulative recurrence rate was 27.0%, while local recurrence was not found in any lesion that lacked these risk factors. Most episodes of recurrence were found during the first or second follow-up endoscopic biopsy at the ulcer scar. Conclusions: Routine follow-up biopsies at the ER site might be unnecessary in cases where an EGC lesion was endoscopically resected en bloc with tumor-free lateral and deep margins.

Purpose: Local recurrence, due to residual tumor, may occur after endoscopic resection for early gastric cancer. The aims of this study are to evaluate the predictive factors for local recurrence, and suggest an appropriate follow-up biopsy strategy. Materials and Methods: We retrospectively reviewed 396 early gastric cancers from 372 consecutive patients, who underwent endoscopic resection between January 2002 and April 2008. Cumulative recurrence rates were determined by the Kaplan-Meier method, and Cox proportional hazard analysis was used to determine the risk factors for local recurrence. Results: Local recurrence at the endoscopic resection site was found in 17 cases, among the total 396 lesions, during a median follow-up period of 48 months. The 5-year cumulative local recurrence rate was 4.8%. Multivariate analyses determined that tumor involvement at the lateral resection margin [hazard ratio: 35.9; P

Background and Objective: Increasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylori (H. pylori)-induced inflammation and may influence susceptibility to developing noncardia gastric cancer. Therefore, we investigated the effect of polymorphisms of TLR2, TLR4, and CD14, their combination and interaction with environmental factors on the noncardia gastric cancer risk in a Korean population. Methods: We genotyped four polymorphisms in three genes (TLR2, rs1898830 A>G; TLR4, rs10759932 T>C, rs10983755 A>G; CD14, rs2569190 T>C) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which was stratified by the histological type of gastric cancer. Results: TLR4 rs10983755 variant allele carriers were found to have a higher risk of intestinal type gastric cancer than homozygous wild-type carriers (OR [95% CI] = 1.40 [1.01–1.96], P = 0.046). Other genetic variants did not show any association with noncardia gastric cancer risk. When we examined the combined effect with other polymorphisms, the increased risk of intestinal type gastric cancer among TLR4 rs10983755 variant allele carriers compared to wild-type homozygous carriers were observed only among homozygous wild-type carriers of TLR2 rs1898830 (OR [95% CI] = 1.97 [1.24–3.12], P = 0.004) or CD14 rs2569190 (OR [95% CI] = 1.95 [1.31–2.91], P = 0.001). In addition, the effect of TLR4 rs10983755 variant allele on intestinal type gastric cancer was stronger among H. pylori-positive participants who are under 55 years old, smoke tobacco and drink alcoholic beverages. Conclusion: These results suggest that the genetic polymorphisms of these innate immunity genes are associated with the development of H. pylori-associated noncardia gastric cancer. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A64.

Introduction: S-1 contains tegafur, which is converted to 5-fluorouracil by CYP2A6. We evaluated the association between polymorphisms of CYP2A6, ERCC1 and XRCC1 and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin. Methods: Among chemonaive MGC patients (n=108) who received S-1 40 mg/m2 b.i.d. on days 1-14 and cisplatin 60 mg/m2 on day 1 of a 3-week cycle, we analyzed the wild-type allele [W] (CYP2A6*1), four CYP2A6 variants [V] that abolish (CYP2A6*4) or reduce (CYP2A6*7, *9, *10) enzyme activity, and the polymorphisms of ERCC1 [8525C>T (rs11615), 19442C>A (rs3212986)] and XRCC1 [1196G>A (rs25487)]. Results: Patients having fewer CYP2A6 variants had significantly better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4 = 66.7% vs 58.3% vs 32.3%; P=0.008), time to progression (TTP) (median, 7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (median, 23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (median, 4.4 vs 7.6 vs 7.9 months) (P=0.012). When we classified patients according to the number of risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C), patients carrying two vs those carrying none showed an adjusted odds ratio of 0.113 (95% CI, 0.025-0.509) (P=0.004) for response and adjusted hazard ratios of 3.748 (95% CI, 1.900-7.393) (P=0.0001) for TTP and 2.961 (95% CI, 1.371-6.393) (P=0.006) for death.Conclusion: CYP2A6 and ERCC1 19442C>A polymorphisms are important predictors for the efficacy of S-1/cisplatin in MGC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5450. doi:10.1158/1538-7445.AM2011-5450

Background: Genetic variations of interleukin-10 (IL-10) and environmental factors are assumed to influence inflammation and gastric carcinogenesis. Therefore, we aimed to investigate the association between IL-10 polymorphisms, smoking, and Helicobacter pylori (H. pylori) infection on the noncardia gastric carcinogenesis in Koreans. Methods: We genotyped 3 promoter polymorphisms (−1082 A>G, -819T>C, -592A>C) on the IL-10 gene in 495 noncardia gastric cancer patients and 495 sex- and age-matched controls. Multiple logistic regression models were used to detect the effects of IL-10 genetic variants, smoking, and H. pylori infection on gastric cancer risk, stratified by histological type of gastric cancer. Results: The IL-10-819C allele and -592C allele are in complete linkage disequilibrium, and IL-10-819C/-592C carriers are associated with a higher risk of noncardia gastric cancer, particularly with a risk of intestinal type cancer (OR [95% CI] = 1.50 [1.08−2.08]), than those with the wild type homozygote genotypes. Compared to nonsmokers carrying the wild type homozygotes, current smokers carrying IL-10-1082G and -819C/-592C showed 4.91 (95% CI = 2.49−9.69) and 6.82 (95% CI = 2.94−15.84) times increased risk of intestinal type gastric cancer, respectively. In addition, smokers with H. pylori infection were in the highest risk of intestinal gastric cancer compared with non-smokers without H. pylori infection, and this association was particularly stronger among IL-10-1082G carriers than AA carriers (OR [95% CI] = 15.54 [5.52−43.72]). Conclusion: Inflammation-related genetic variants may interact with smoking and H. pylori infection on the risk of noncardia gastric cancer, particularly intestinal type. Therefore, high risk group may reduce the risk of gastric cancer by modifying their lifestyles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3745. doi:10.1158/1538-7445.AM2011-3745

Introduction: This study investigated the efficacy and safety of S-1 plus irinotecan and oxaliplatin (TIROX) in metastatic gastric cancer (MGC) and examined the association between uridine diphosphate-glucuronosyltransferase (UGT) 1A polymorphisms and treatment outcomes. Methods: Patients with previously untreated MGC received S-1 40 mg/m2 b.i.d. on days 1-14, irinotecan 150 mg/m2 and oxaliplatin 85 mg/m2 on day 1 every 3 weeks. We analyzed the association of UGT1A genotypes and clinical outcomes. Results: Forty-four patients were enrolled on study and received a median of 11 cycles (range, 1-12). Of the 42 patients assessable for response, the objective response rate was 79% (95% CI, 66% to 91%); complete response (CR) (14%) and partial response (64%). The median time to progression (TTP) and overall survival (OS) was 10.2 months (95% CI, 7.7 to 12.7) and 17.6 months (95% CI, 9.0 to 26.2), respectively. Ten (26%) of 39 patients with primary gastric tumor showed a biopsy-proven gastric CR. Grade 3/4 neutropenia developed in 66% of patients and grade 3 febrile neutropenia in 16%. Non-hematological toxicities were modest and manageable. The most common grade 3 non-hematological toxicity was abdominal pain (18%), followed by anorexia (16%) and diarrhea (14%). UGT1A polymorphisms was associated with significantly higher incidence of grade 4 leukopenia (UGT1A1*6), neutropenia (UGT1A1*6, UGT1A6*2, or UGT1A7*3), grade 3/4 febrile neutropenia (UGT1A1*6), or grade 3 abdominal pain (UGT1A1*6). Conclusions: TIROX is a highly active regimen inducing marked tumor reduction and promising survival with a manageable toxicity profile in MGC patients. Genotyping for UGT1A might predict severe toxicity for TIROX.Association of UGT1A Genotypes with Toxicity during Cycle 1 G4 leukopeniaG4 neutropeniaG3/4 febrile neutropeniaG3 abdominal pain No.(%)PNo.(%)PNo.(%)PNo.(%)PUGT1A1*6 0.042 0.013 0.042 0.042absence0/28 (0) 0/28 (0) 0/28 (0) 0/28 (0) presence3/16 (19) 4/16 (25) 3/16 (19) 3/16 (19) UGT1A1*28 1.000 1.000 1.000 1.000absence3/35 (9) 3/35 (9) 3/35 (9) 3/35 (9) presence0/9 (0) 1/9 (11) 0/9 (0) 0/9 (0) UGT1A1*60 0.258 0.634 0.258 0.258absence3/26 (12) 3/26 (12) 3/26 (12) 3/26 (12) presence0/18 (0) 1/18 (6) 0/18 (0) 0/18 (0) UGT1A6*2 0.100 0.044 0.100 0.100absence0/23 (0) 0/23 (0) 0/23 (0) 0/23 (0) presence3/21 (14) 4/21 (19) 3/21 (14) 3/21 (14) UGT1A7*3 0.100 0.044 0.100 0.100absence0/23 (0) 0/23 (0) 0/23 (0) 0/23 (0) presence3/21 (14) 4/21 (19) 3/21 (14) 3/21 (14) Toxicity grade by National Cancer Institute Common Toxicity Criteria version 3.0 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3719.

4628 Background: A prospective high-throughput gene expression study was conducted to identify transcriptional profiles predictive of a clinical response to cisplatin and fluorouracil (CF) combination chemotherapy and to identify dysregulated genes associated with acquired resistance to CF. Methods: Endoscopic biopsy samples were collected from CF-treated metastatic gastric cancer (MGC) patients (pts) prior to CF (n = 123) and following the development of resistance (n = 22) at the National Cancer Center of Korea from 2001 to 2006, and analyzed using CGH and expression microarrays. We developed 2 survival risk predictors. The first predictor was constructed using genes in DNA amplicons and identified in the expression signature that correlates with survival (intrinsic resistance signature). The second predictor was based on the acquired resistance signature, which was identified by comparing matched expression array data from initially responsive patients prior to treatment with profiles obtained at progressive disease. Results: Array CGH revealed the gene amplification of MYC, EGFR, and FGFR2 whose Affymetrix U133A signals significantly correlated with a poor prognosis (P values, 0.0154, 0.0096, and 0.0057) of training set pts (n = 96). Three-gene-predicted high-risk group of the validation cohort (n = 10) demonstrated a shorter median survival than low-risk (n = 17) group (7.4 vs 16.8 months; p = 0.047). The 3-gene signature, as a continuous variable, was the independent predictor for overall survival (OS) and time to progression (TTP) (adjusted P, 0.021, and 0.012). Importantly, the acquired resistance signature strongly overlapped the intrinsic resistance signature (LS P-5), and was highly enriched for MYC target genes (LS p = 2x10-5). A predictor based on MYC target genes within the acquired resistance signature was the independent predictor for OS and TTP of 101 separate pts (adjusted p, 0.015, and 0.011). Conclusions: Combined overexpression of MYC, EGFR, and FGFR2 predicts a poor response of MGC pts to CF. There is significant overlap between intrinsic and acquired resistance signatures of MGC, where the MYC gene network plays a central role. This is the first demonstration that the acquired resistance signature predicts the initial response to chemotherapy. No significant financial relationships to disclose.

Purpose: The prognosis for patients with liver metastases (LM) from colorectal cancer is significantly influenced by the clinician’s decision. Recently, there have been remarkable advances in treatment of LM, so there can be some changes in therapeutic modalities. We performed a comparative study between operated and non- operated groups of patients with LM to analyze the clinical outcome. Methods: From Feb. 2001 to Feb. 2006, 27 patients with LM underwent a hepatectomy, and 113 patients received non-surgical therapy. thirteen hepatectomized cases among the 27 patients had multiple LM. The outcomes of those 13 patients (Group A) were retrospectively compared to those of the non- operated group (Group B, n=21), which had had potentially resectable LM at the initial diagnosis or after chemotherapy, but didn’t undergo hepatic resection. Results: After a median follow-up duration of 31.3 months, the estimated 3-years overall survival (OS) rates were 76.9% and 14.3% in group A and B, respectively (P=0.0001). In the stepwise Cox multivariate regression analysis, factors such as the absence of hepatic resection and a greater diameter of the liver mass independently influenced the poor survival (P=0.005 and P=0.012 respectively). Additionally, two radiologists evaluated the intraoperative ultrasonographic (IOUS) results. IOUS detected new metastatic lesions in 4/13 (30%) patients. There were sub-centimeter metastatic lesions (5∼7 mm) and had not been detected in SPIO-enhanced MRI. Conclusions: Our results compared to palliative chemotherapy suggest that aggressive surgical resection should be performed to increase the survival rate in patients with LM. Additionally, the treatment plan for LM patients should be discussed with the gastroenterololgist, the radiologist, the oncologist, and the surgeon.

AIM: To identify patients with a high-risk of having a synchronous cancer among gastric cancer patients. METHODS: We retrospectively analyzed the prospective gastric cancer database at the National Cancer Center, Korea from December 2000 to December 2004. The clinicopathological characteristics of patients with synchronous cancers and those of patients without synchronous cancers were compared. Multivariate analysis was performed to identify the risk factors for the presence of a synchronous cancer in gastric cancer patients. RESULTS: 111 of 3 291 gastric cancer patients (3.4%) registered in the database had a synchronous cancer. Among these 111 patients, 109 had a single synchronous cancer and 2 patients had two synchronous cancers. The most common form of synchronous cancer was colorectal cancer (42 patients, 37.2%) followed by lung cancer (21 patients, 18.6%). Multivariate analyses revealed that elderly patients with differentiated early gastric cancer have a higher probability of a synchronous cancer. CONCLUSION: Synchronous cancers in gastric cancer patients are not infrequent. The physicians should try to find synchronous cancers in gastric cancer patients, especially in the elderly with a differentiated early gastric cancer.