- Email: [email protected]
Su1977 Accuracy of Multidetector-Row Computed Tomography (MDCT) for Clinical N Staging in Early Gastric Cancer
truncating protein predicted by SHIFT. One CIMP-positive case also presented PIK3CA missense mutation affecting helical domain (E545A). Conclusion: Typical endoscopic appearances of EBV-positive GCs are depressed (0-IIc, 0-IIc+III) or depressed with surrounding elevation (0-IIa+IIc) for early cases and ulcerative form (type 2 or 3) for advanced cases. Prevalence, clinical and molecular features of EBV-positive GCs (gender, location, CIMP positivity) were in line with previous report, while it was also revealed that subset of EBVpositive cases show mutations in TP53 and PIK3CA. The fact that pathologically superficial cancer presented differentiated histologic type suggests that majority of the EBV-positive cases may have originally developed as differentiated type histopathology.
Su1975 Su1977
Gastric Intestinal Metaplasia and Risk of Gastric Cancer in a Diverse Integrated Healthcare Setting Kavya Reddy, Bechien U. Wu, Wei Yu, Judith D. Bebchuk
Accuracy of Multidetector-Row Computed Tomography (MDCT) for Clinical N Staging in Early Gastric Cancer Eun Hyo Jin, Dong Ho Lee, Ji Yeon Seo, Jaihwan Kim, Young Su Park, Cheol Min Shin, Hyuk Yoon, Jin-hyeok Hwang, Nayoung Kim
Background: Gastric intestinal metaplasia (GIM) is a common finding on routine endoscopy. Although GIM is an established early step in gastric carcinogenesis, controversy exists regarding whether routine surveillance should be performed in individuals with GIM in low prevalence regions such as the United States. Objective: Our study aims were to 1) determine frequency of gastric cancer among patients with GIM in a large diverse integrated healthcare setting and 2) evaluate risk factors for gastric cancer in this patient population. Methods: We conducted a retrospective cohort study using data from an integrated health system in Southern California between 2000 and 2011. Patients with GIM identified on endoscopic biopsy were identified by key word search of pathology reports. Individual pathology reports were manually reviewed to confirm the diagnosis of GIM. Cases of gastric cancer were identified by cross-reference with a prospectively collected internal gastric cancer registry. Patients with history of gastric cancer diagnosed prior to detection of GIM were excluded. Patients with gastric cancer diagnosed within 30 days of GIM were considered to have gastric cancer present at the time of initial diagnosis. Risk factors for gastric cancer examined in the study included race/ethnicity, smoking status, H. pylori status, family history of gastric cancer, and body mass index. Results: We identified a total of 935 patients with GIM on routine endoscopy during the study period. Eleven patients were excluded based on prior history of gastric cancer. Among the remaining 924 patients, median age at diagnosis was 68.1 years (interquartile range IQR 58.3, 76.3). Median duration of follow-up was 4.6 years (IQR 3.0, 6.7). There were a total of 26 cancers detected during the study period. Seventeen [65%] of cancers were diagnosed at the time of GIM and 9 [35%] cancers were diagnosed after GIM. For those cancers diagnosed after GIM, the median time until diagnosis of cancer was 55 months (IQR 24, 68). Mortality among patients with gastric cancer was 50%. Among the risk factors we evaluated, only family history was associated with increased risk of gastric cancer in this cohort (odds-ratio 3.8 [95% CL 1.5, 9.7]), χ2 p=0.012). Conclusions: Among patients with gastric intestinal metaplasia, 2.8% had gastric cancer diagnosed during the study period. The majority of cancers were present at the time of GIM diagnosis. Of the risk factors evaluated, family history was the only risk factor associated with a statistically significant increase in gastric cancer. Given the high mortality among patients with gastric cancer, surveillance of patients with both GIM and a family history of gastric cancer could potentially lead to improvement in survival based on earlier detection. Risk Factors for Gastric Cancer
Background: An accurate preoperative assessment of potential lymph node metastasis is useful in the decision for the treatment strategy of early gastric cancer. The aims of this retrospective study were to determine the accuracy of multidetector-row computed tomography (MDCT) for clinical N staging in early gastric cancer and to investigate the clinicopathological factors affecting the diagnostic accuracy. Methods: We had analyzed 1097 patients with early gastric cancer who underwent gastrectomy with lymph-node dissection at Seoul National University Bundang Hospital from May 2003 to July 2011. All patients underwent preoperative MDCT. Lymph nodes were considered positive for metastasis if they were equal to or larger than 8mm in the short axis diameter of MDCT. The clinical N staging from the preoperative MDCT was compared to the postoperative pathological finding. Results: The overall diagnostic sensitivity, specificity, and accuracy of MDCT for determining lymph node metastasis were 14.4%, 89.1%, and 82.0%, respectively. The rate of overestimation (108/ 1097, 9.8%) was higher than the rate of underestimation for clinical N staging (89/1097, 8.1%). Univariate analysis showed that the following factors were significant clinicopathological factors affecting underestimation for clinical N staging; gender (female) (p=0.010), undifferentiated histology (p=0.009), submucosal invasion (p<0.0001), large tumor size (>2cm) (p<0.0001), depressed type (p=0.001) and lymphovascular invasion (p<0.0001). Multivariate analysis showed that underestimation of clinical N staging was related with tumor size (>2cm) (p=0.001, OR=5.066), lymphovascular invasion (p=0.001, OR=3.173). On univariate analysis, submucosal invasion, tumor size (>2cm) were significant factors affecting overestimation for clinical N staging (p=0.029, p=0.002). On multivariate, tumor size (>2cm) was an independent factors for overestimation of clinical N staging (p=0.008, OR=1.817). Conclusions: For preoperative assessment of lymph node metastasis in early gastric cancer, MDCT is showed high specificity but low sensitivity. Although diagnostic accuracy of clinical N staging by MDCT is not poor, the rate of underestimation and overestimation were 8.1% and 9.8%. Large tumor size (>2cm) and lymphovascular invasion were related to underestimation of clinical N staging. Large tumor size (>2cm) was related to overestimation of clinical N staging in early gastric cancer. We proposed that careful attention is required to choose treatment based on clinical N staging by MDCT, especially large sized tumor and lymphovascular invasion. Su1979 Adenocarcinomas at the Esophagogastric Junction At the Most Distal Location (Siewert Type 3) are More Likely Associated With Preneoplastic Mucosal Changes in the Stomach Than Proximal Tumors Jan Bornschein, Michael Selgrad, Andrea Dingwerth, Marino Venerito, Katrin Frauenschlaeger, Peter Malfertheiner
Univariate Analysis n=924, 26 gastric cancers
Background/Aim: Adenocarcinomas at the esophagogastric junction (AEG) are either related to gastroesophageal reflux disease or to H. pylori infection and associatedchanges in the gastric mucosa. For the majority of junctional cancers, the mucosa of the gastric body and antrum are not affected by malignant infiltration. These areas are assessed for staging of premalignant risk according to the presence and severity of glandular atrophy (Operative Link for Gastritis Assessment: OLGA staging) or intestinal metaplasia (IM, OLGIM staging). We aimed to compare the OLGA and OLGIM stages for AEG of different location (Siewert type). Patients and Methods: We included 164 patients with AEG, subdivided into: main tumor mass in the distal esophagus (AEG1: n=48), at the esophagogastricjunction (AEG2: n=54), or in the proximal stomach (AEG3: n=62). Mean age were 66.5+/- 11.70 years, 137 were male (83.5%). Laurén type was intestinal for 136 patients (82.9%), 28 showed diffuse or mixed differentiation (17.1%). Fisher's exact and Chi-square test were applied for comparison of categorical variables, Kruskal-Wallis and Mann Whitney U test for comparison of histology scores. Results: OLGA stage could be assessed in 131 patients (79.9%), OLGIM in 139 (84.8%). For the remaining patients, assessment of atrophy or IM was not given or incomplete for antrum or corpus. The distribution of OLGA and OLGIM stages between AEG of different location were significantly different (Table). Both AEG2 and AEG3 showed higher OLGA and OLGIM stages than AEG1. AEG3 showed higher OLGIMstages compared with AEG2, but similar OLGA stages. Mean scores for atrophy were significantly different for the AEG, for both antrum (AEG1: 0.09+0.358; AEG2: 0.32+0.695; AEG3: 0.48+0.875) and corpus (AEG1: 0.00; AEG2: 0.21+0.667; AEG3: 0.35+0.779). This was also the case for IM in antrum (AEG1: 0.13+0.40; AEG2: 0.40+0.782; AEG3: 0.78+0.816) and corpus (AEG1: 0.06+0.433; AEG2: 0.20+0.495; AEG3: 0.50+0.863). AEG1 showed only intestinal type cancers whereas there were mixed/diffuse type cancers in 22.2% of AEG2 and 25.8% of AEG3. There was no difference between the AEG concerning gender and H. pylori status. Conclusion: Distal cancers at the esophagogastric junction (AEG3) are associated with higher OLGA and OLGIM stages compared to AEG1.For a majority of junctional cancers an assessment of OLGA or OLGIM staging is possible. OLGA and OLGIM stages for adenocarcinomas at the esophagogastric junction
Su1976 Endoscopic, Clinic-Pathological and Molecular Features of Epstein-Barr Virus (EB) Positive Gastric Carcinoma Tomomitsu Tahara, Tomoyuki Shibata, Masaaki Okubo, Kazuya Sumi, Takamitsu Ishizuka, Yuichiro Ichikawa, Tomohiko Kawamura, Masakatsu Nakamura, Mitsuo Nagasaka, Yoshihito Nakagawa, Naoki Ohmiya, Tomiyasu Arisawa, Ichiro Hirata Background/Aim: Epstein-Barr virus (EBV) infection is involved in a subset of gastric carcinomas (GCs), providing distinct clinical and molecular features. We performed prevalence screening of EBV using surgically or endoscopically obtained GC specimens in our hospital and correlated with endoscopic, clinic-pathological and molecular features. Method: In total of 217 GCs were examined for the presence of EBV genome. The specimens were first screened for the presence of the EBV genome by PCR with primers specific the EBV BamHI W region. Then, the result was confirmed by real-time quantitative PCRs with dual-labeled fluorogenic hybridization probes (one toward the BamHI-W region; and the other toward the EBNA-1 region). For EBV positive (EBV+) cases, mutations of TP53, KRAS, PIK3CA were examined. The status of CpG island methylator phenotype (CIMP) was also examined using 13 panels of genes (MINT1, 2, 12, 25 and 31, RORA, GDNF, ADAM23, MLF1, PRDM5, RASSF1A, ATP2B4 and MLH1). Result: Among the 217 GC cases, presence of EBV was confirmed in ten cases (4.6%). Nine of the ten cases were male) and median age was 57 years old. All cases located middle or upper third in the stomach with multiple lesions for three cases. Typical endoscopic appearances in the early cases are depressed (0-IIc, 0IIc+III) or depressed with surrounding elevation (0-IIa+IIc). Two out of three pathologically superficial carcinomas (T1a) presented differentiated histologic type (well or moderately differentiated adenocarcinomas), while all cases invading into SM2 or deeper showed poorly differentiated adenocarcinomas. Typical endoscopic appearances for advanced cases were ulcerative lesions (type 2 or 3). Eight out of ten cases presented CIMP showing dense methylation in all markers examined, except for MLH1. Two CIMP-positive cases presented missense mutation in TP53, one was within hot-spot lesion in DNA-binding domain (R175H) and the other was in the novel position in DNA-binding domain (D259Y), resulting in
S-513
AGA Abstracts
AGA Abstracts
advanced AJCC stages (p<0.001). Patients with lower IGFBP-2 levels had better survival than those with higher IGFBP2 tertile levels (Hazard Ratio =1.28, 95% CI=1.05-1.57, p= 0.014) after adjustment for age, gender, and AJCC stage. However, the survival was not significantly differed according to plasma IGF2 levels. Conclusion: Plasma level of IGFBP2 was higher in patients with gastric cancer and correlated with stage and is a potential prognostic marker for gastric cancer. Key words: gastric cancer, IGF2, IGFBP2, survival, prognosis
Su1975 Su1977
Gastric Intestinal Metaplasia and Risk of Gastric Cancer in a Diverse Integrated Healthcare Setting Kavya Reddy, Bechien U. Wu, Wei Yu, Judith D. Bebchuk
Accuracy of Multidetector-Row Computed Tomography (MDCT) for Clinical N Staging in Early Gastric Cancer Eun Hyo Jin, Dong Ho Lee, Ji Yeon Seo, Jaihwan Kim, Young Su Park, Cheol Min Shin, Hyuk Yoon, Jin-hyeok Hwang, Nayoung Kim
Background: Gastric intestinal metaplasia (GIM) is a common finding on routine endoscopy. Although GIM is an established early step in gastric carcinogenesis, controversy exists regarding whether routine surveillance should be performed in individuals with GIM in low prevalence regions such as the United States. Objective: Our study aims were to 1) determine frequency of gastric cancer among patients with GIM in a large diverse integrated healthcare setting and 2) evaluate risk factors for gastric cancer in this patient population. Methods: We conducted a retrospective cohort study using data from an integrated health system in Southern California between 2000 and 2011. Patients with GIM identified on endoscopic biopsy were identified by key word search of pathology reports. Individual pathology reports were manually reviewed to confirm the diagnosis of GIM. Cases of gastric cancer were identified by cross-reference with a prospectively collected internal gastric cancer registry. Patients with history of gastric cancer diagnosed prior to detection of GIM were excluded. Patients with gastric cancer diagnosed within 30 days of GIM were considered to have gastric cancer present at the time of initial diagnosis. Risk factors for gastric cancer examined in the study included race/ethnicity, smoking status, H. pylori status, family history of gastric cancer, and body mass index. Results: We identified a total of 935 patients with GIM on routine endoscopy during the study period. Eleven patients were excluded based on prior history of gastric cancer. Among the remaining 924 patients, median age at diagnosis was 68.1 years (interquartile range IQR 58.3, 76.3). Median duration of follow-up was 4.6 years (IQR 3.0, 6.7). There were a total of 26 cancers detected during the study period. Seventeen [65%] of cancers were diagnosed at the time of GIM and 9 [35%] cancers were diagnosed after GIM. For those cancers diagnosed after GIM, the median time until diagnosis of cancer was 55 months (IQR 24, 68). Mortality among patients with gastric cancer was 50%. Among the risk factors we evaluated, only family history was associated with increased risk of gastric cancer in this cohort (odds-ratio 3.8 [95% CL 1.5, 9.7]), χ2 p=0.012). Conclusions: Among patients with gastric intestinal metaplasia, 2.8% had gastric cancer diagnosed during the study period. The majority of cancers were present at the time of GIM diagnosis. Of the risk factors evaluated, family history was the only risk factor associated with a statistically significant increase in gastric cancer. Given the high mortality among patients with gastric cancer, surveillance of patients with both GIM and a family history of gastric cancer could potentially lead to improvement in survival based on earlier detection. Risk Factors for Gastric Cancer
Background: An accurate preoperative assessment of potential lymph node metastasis is useful in the decision for the treatment strategy of early gastric cancer. The aims of this retrospective study were to determine the accuracy of multidetector-row computed tomography (MDCT) for clinical N staging in early gastric cancer and to investigate the clinicopathological factors affecting the diagnostic accuracy. Methods: We had analyzed 1097 patients with early gastric cancer who underwent gastrectomy with lymph-node dissection at Seoul National University Bundang Hospital from May 2003 to July 2011. All patients underwent preoperative MDCT. Lymph nodes were considered positive for metastasis if they were equal to or larger than 8mm in the short axis diameter of MDCT. The clinical N staging from the preoperative MDCT was compared to the postoperative pathological finding. Results: The overall diagnostic sensitivity, specificity, and accuracy of MDCT for determining lymph node metastasis were 14.4%, 89.1%, and 82.0%, respectively. The rate of overestimation (108/ 1097, 9.8%) was higher than the rate of underestimation for clinical N staging (89/1097, 8.1%). Univariate analysis showed that the following factors were significant clinicopathological factors affecting underestimation for clinical N staging; gender (female) (p=0.010), undifferentiated histology (p=0.009), submucosal invasion (p<0.0001), large tumor size (>2cm) (p<0.0001), depressed type (p=0.001) and lymphovascular invasion (p<0.0001). Multivariate analysis showed that underestimation of clinical N staging was related with tumor size (>2cm) (p=0.001, OR=5.066), lymphovascular invasion (p=0.001, OR=3.173). On univariate analysis, submucosal invasion, tumor size (>2cm) were significant factors affecting overestimation for clinical N staging (p=0.029, p=0.002). On multivariate, tumor size (>2cm) was an independent factors for overestimation of clinical N staging (p=0.008, OR=1.817). Conclusions: For preoperative assessment of lymph node metastasis in early gastric cancer, MDCT is showed high specificity but low sensitivity. Although diagnostic accuracy of clinical N staging by MDCT is not poor, the rate of underestimation and overestimation were 8.1% and 9.8%. Large tumor size (>2cm) and lymphovascular invasion were related to underestimation of clinical N staging. Large tumor size (>2cm) was related to overestimation of clinical N staging in early gastric cancer. We proposed that careful attention is required to choose treatment based on clinical N staging by MDCT, especially large sized tumor and lymphovascular invasion. Su1979 Adenocarcinomas at the Esophagogastric Junction At the Most Distal Location (Siewert Type 3) are More Likely Associated With Preneoplastic Mucosal Changes in the Stomach Than Proximal Tumors Jan Bornschein, Michael Selgrad, Andrea Dingwerth, Marino Venerito, Katrin Frauenschlaeger, Peter Malfertheiner
Univariate Analysis n=924, 26 gastric cancers
Background/Aim: Adenocarcinomas at the esophagogastric junction (AEG) are either related to gastroesophageal reflux disease or to H. pylori infection and associatedchanges in the gastric mucosa. For the majority of junctional cancers, the mucosa of the gastric body and antrum are not affected by malignant infiltration. These areas are assessed for staging of premalignant risk according to the presence and severity of glandular atrophy (Operative Link for Gastritis Assessment: OLGA staging) or intestinal metaplasia (IM, OLGIM staging). We aimed to compare the OLGA and OLGIM stages for AEG of different location (Siewert type). Patients and Methods: We included 164 patients with AEG, subdivided into: main tumor mass in the distal esophagus (AEG1: n=48), at the esophagogastricjunction (AEG2: n=54), or in the proximal stomach (AEG3: n=62). Mean age were 66.5+/- 11.70 years, 137 were male (83.5%). Laurén type was intestinal for 136 patients (82.9%), 28 showed diffuse or mixed differentiation (17.1%). Fisher's exact and Chi-square test were applied for comparison of categorical variables, Kruskal-Wallis and Mann Whitney U test for comparison of histology scores. Results: OLGA stage could be assessed in 131 patients (79.9%), OLGIM in 139 (84.8%). For the remaining patients, assessment of atrophy or IM was not given or incomplete for antrum or corpus. The distribution of OLGA and OLGIM stages between AEG of different location were significantly different (Table). Both AEG2 and AEG3 showed higher OLGA and OLGIM stages than AEG1. AEG3 showed higher OLGIMstages compared with AEG2, but similar OLGA stages. Mean scores for atrophy were significantly different for the AEG, for both antrum (AEG1: 0.09+0.358; AEG2: 0.32+0.695; AEG3: 0.48+0.875) and corpus (AEG1: 0.00; AEG2: 0.21+0.667; AEG3: 0.35+0.779). This was also the case for IM in antrum (AEG1: 0.13+0.40; AEG2: 0.40+0.782; AEG3: 0.78+0.816) and corpus (AEG1: 0.06+0.433; AEG2: 0.20+0.495; AEG3: 0.50+0.863). AEG1 showed only intestinal type cancers whereas there were mixed/diffuse type cancers in 22.2% of AEG2 and 25.8% of AEG3. There was no difference between the AEG concerning gender and H. pylori status. Conclusion: Distal cancers at the esophagogastric junction (AEG3) are associated with higher OLGA and OLGIM stages compared to AEG1.For a majority of junctional cancers an assessment of OLGA or OLGIM staging is possible. OLGA and OLGIM stages for adenocarcinomas at the esophagogastric junction
Su1976 Endoscopic, Clinic-Pathological and Molecular Features of Epstein-Barr Virus (EB) Positive Gastric Carcinoma Tomomitsu Tahara, Tomoyuki Shibata, Masaaki Okubo, Kazuya Sumi, Takamitsu Ishizuka, Yuichiro Ichikawa, Tomohiko Kawamura, Masakatsu Nakamura, Mitsuo Nagasaka, Yoshihito Nakagawa, Naoki Ohmiya, Tomiyasu Arisawa, Ichiro Hirata Background/Aim: Epstein-Barr virus (EBV) infection is involved in a subset of gastric carcinomas (GCs), providing distinct clinical and molecular features. We performed prevalence screening of EBV using surgically or endoscopically obtained GC specimens in our hospital and correlated with endoscopic, clinic-pathological and molecular features. Method: In total of 217 GCs were examined for the presence of EBV genome. The specimens were first screened for the presence of the EBV genome by PCR with primers specific the EBV BamHI W region. Then, the result was confirmed by real-time quantitative PCRs with dual-labeled fluorogenic hybridization probes (one toward the BamHI-W region; and the other toward the EBNA-1 region). For EBV positive (EBV+) cases, mutations of TP53, KRAS, PIK3CA were examined. The status of CpG island methylator phenotype (CIMP) was also examined using 13 panels of genes (MINT1, 2, 12, 25 and 31, RORA, GDNF, ADAM23, MLF1, PRDM5, RASSF1A, ATP2B4 and MLH1). Result: Among the 217 GC cases, presence of EBV was confirmed in ten cases (4.6%). Nine of the ten cases were male) and median age was 57 years old. All cases located middle or upper third in the stomach with multiple lesions for three cases. Typical endoscopic appearances in the early cases are depressed (0-IIc, 0IIc+III) or depressed with surrounding elevation (0-IIa+IIc). Two out of three pathologically superficial carcinomas (T1a) presented differentiated histologic type (well or moderately differentiated adenocarcinomas), while all cases invading into SM2 or deeper showed poorly differentiated adenocarcinomas. Typical endoscopic appearances for advanced cases were ulcerative lesions (type 2 or 3). Eight out of ten cases presented CIMP showing dense methylation in all markers examined, except for MLH1. Two CIMP-positive cases presented missense mutation in TP53, one was within hot-spot lesion in DNA-binding domain (R175H) and the other was in the novel position in DNA-binding domain (D259Y), resulting in
S-513
AGA Abstracts
AGA Abstracts
advanced AJCC stages (p<0.001). Patients with lower IGFBP-2 levels had better survival than those with higher IGFBP2 tertile levels (Hazard Ratio =1.28, 95% CI=1.05-1.57, p= 0.014) after adjustment for age, gender, and AJCC stage. However, the survival was not significantly differed according to plasma IGF2 levels. Conclusion: Plasma level of IGFBP2 was higher in patients with gastric cancer and correlated with stage and is a potential prognostic marker for gastric cancer. Key words: gastric cancer, IGF2, IGFBP2, survival, prognosis