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Background: The incidence of gastric cancer increases in the remnant stomach after partial gastrectomy, however, its pathogenesis remains controversial. The clinicopathological features and immunohistochemical subtype were evaluated in patients with remnant gastric cancer considering the initial cause of partial gastrectomy. Methods: We categorized 59 cases of remnant gastric cancer who underwent curative surgery between 2001 and 2016 according to initial pathologies of benign (n = 24) or malignant (n = 35). Histological changes including pyloric metaplasia and intestinal metaplasia in the mucosa around the anastomosis site and the background mucosa of carcinomas were compared between the groups. Results: In the malignant group, the proportion of male patients was substantially lower, with a shorter interval. In background mucosa around the carcinomas, incidence of high-grade pyloric metaplasia was significantly higher in the benign group (13/20, 65.0% vs. 10/28, 35.7%), while high-grade intestinal metaplasia was only observed in the malignant group (0/20, 0% vs. 7/28, 25.0%). Conclusions: The cancers in the initial benign disease are mainly associated with pyloric metaplasia at the anastomosis site, reflecting reflux, but not with intestinal metaplasia. On the other hand, in the initial malignant disease group, intestinal metaplasia has an equally important role as reflux-associated pyloric metaplasia.

Intestinal-type gastric cancer often results from

e16580 Background: Gastric cancer subtyping system such as Lauren classification is widely used in clinical practice since it is an independent prognostic factor, and also provides the basis for individualized treatment. However, Lauren classification showed low reproducibility because it is based on qualitative method. Thus, a more reproducible system has been required. In this study, we explore the concordance between a cancer detection model (CDM)-based unsupervised subtyping and a current classification system. Methods: We focused on Lauren classification since it has relatively simple major subtypes: intestinal and diffuse types. 88 resection cases of gastric cancer are collected. Two experienced gastrointestinal pathologists evaluated each case independently by Lauren’s criteria. 200 cancer region image patches per case and its features extracted by the CDM were clustered into five groups via k-means clustering. We then defined the ratio of the number of patches in each cluster group as the case-level feature. Cases are clustered into two groups via k-means clustering using the features. We named this case-level clustering result as a deep learning-based subtyping (DLS), hereafter. Results: DLS showed a high correlation with Lauren classification: intestinal and diffuse subtype. The kappa scores between the pathologists and algorithm (0.765 and 0.796) were higher than between pathologists (0.700). The cluster centers corresponding to intestinal and diffuse types were [44.6, 21.5, 47.5, 63.7, 22.7] and [35.5, 148.2, 4.0, 9.0, 2.3], respectively. Further review of the patches contributing to the second feature (21.5 and 148.2) confirmed that they demonstrate typical morphological characteristics of diffuse type. Conclusions: Our analysis showed that the morphological characteristics of Lauren classification were inherent in gastric cancer detection task and WSIs can be subtyped by the data-driven, and unsupervised manner. Furthermore, DLS was more reliable than human from the concordance results. This suggests that the DLS can supplement current classification systems or be a new subtyping system. [Table: see text]

Purpose The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. Materials and methods We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. Results The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. Conclusion The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.

Background: Risks and benefits of laparoscopic sentinel node navigation surgery (LSNNS) compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection (LND) for early gastric cancer (EGC) are unknown. The SENORITA trial investigated the clinical impact of LSNNS for EGC regarding short-term surgical outcomes, long-term survival, and quality of life (QOL). Methods: Patients with preoperatively diagnosed T1N0 gastric adenocarcinoma with a diameter of 3 cm or smaller regardless of histology (except absolute indication for endoscopic resection) were eligible. Patients were randomized to LSG with LND or LSNNS. The primary endpoint was 3-year disease-free survival. Morbidity and mortality within 30 postoperative days were evaluated as secondary endpoints and graded by the Clavien-Dindo classification. Findings: From March 2013 to December 2016, 580 patients were randomized (LSG, 292; LSNNS, 288). Fifty-three patients dropped out before surgery due to various reasons. Surgery was performed for 527 patients (LSG, 269; LSNNS, 258) representing the full analysis set. LSNNS was not performed in 13 patients due to intraoperative findings. LSNNS was performed according to protocol for 245 patients, and detection of sentinel basin was possible for 237 patients (96.7%, 237/245). Stomach-preserving surgery was performed in 210 patients (81.4%. 210/258). Postoperative complications occurred in 51 LSG patients (19.0%) and 40 LSNNS patients (15.5%) (P=0.294). Clavien-Dindo grade III or higher complications occurred in 16 LSG patients (5.9%) and 13 LSNNS patients (5.0%) (P=0.647). Postoperative mortality occurred in one LSG patient. LSNNS was not a risk factor for postoperative morbidity in multivariate analysis except sex. Interpretation: LSNNS for EGC is a safe procedure in terms of postoperative morbidity and mortality when compared with LSG with LND. Results: From March 2013 to December 2016, 580 patients were randomized (LSG, 292; LSNNS, 288). Surgery was performed for 527 patients (LSG, 269; LSNNS, 258) representing the full analysis set. LSNNS was not performed in 13 patients due to intraoperative findings. LSNNS was performed according to protocol for 245 patients, and detection of sentinel basin was possible for 237 patients (96.7%, 237/245). Stomach-preserving surgery was performed in 210 patients (81.4%. 210/258). Postoperative complications occurred in 51 LSG patients (19.0%) and 40 LSNNS patients (15.5%) (P=0.294). Clavien-Dindo grade III or higher complications occurred in 16 LSG patients (5.9%) and 13 LSNNS patients (5.0%) (P=0.647). Postoperative mortality occurred in one LSG patient. LSNNS was not a risk factor for postoperative morbidity in multivariate analysis except sex. Conclusions: LSNNS for EGC is a safe procedure in terms of postoperative morbidity and mortality when compared with LSG with LND. Trial Registration Number: NCT01804998. Funding: National Cancer Center, Republic of Korea (grant number: 1710160-2). Declaration of Interest: The authors declare that they have no conflicts of interest or financial ties to disclose. Ethical Approval: All patients provided written informed consent before the surgery. This study was reviewed and approved by the local institutional review boards of all participating institutions.

BACKGROUND: The effect of current infection of Helicobacter pylori on gastric cancer has rarely been studied in a large population. We investigated the association of current H. pylori infection and metabolic factors with gastric cancer in a large population. METHODS: Persons who made their first visit to the National Cancer Center for a health examination, including endoscopy and H. pylori testing using gastric tissue between 2003 and 2013, were included. The association of H. pylori with gastric cancer was estimated using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 35,519 people, 113 gastric cancer and 158 gastric dysplasia cases were detected. In the adjusted analysis, gastric cancer was associated with current H. pylori infection (OR, 2.39; 95% CI, 1.53–3.74), age (OR, 1.06; 95% CI 1.04–1.08), first-degree relatives with gastric cancer (OR, 2.08; 95% CI, 1.30–3.32) and hyperglycaemia (OR, 1.66; 95% CI, 1.04–2.65), whereas it was inversely associated with high-density lipoprotein (HDL) (OR, 0.49; 95% CI, 0.22–0.94). In the subanalysis, gastric cancer was associated with first-degree relatives with gastric cancer (OR, 3.23; 95% CI, 1.39–7.50) in the absence of H. pylori, whereas it was associated with hyperglycaemia (OR, 1.98; 95% CI, 1.16–3.39) in the presence of H. pylori. CONCLUSIONS: Gastric cancer was associated with current H. pylori infection, hyperglycaemia, and low HDL levels in a large population.

We conducted a phase 1 trial for single-dose intravenous Ad5CRT, a replication-defective adenovirus vector expressing HSVtk (herpes simplex virus thymidine kinase) modulated by a specific trans-splicing ribozyme that targets human telomerase reverse transcriptase (hTERT)-encoding RNAs. Dose-limiting toxicities (DLTs) were evaluated in 15 patients at dose levels of 0.1–2 × 1012 virus particles. Patients well tolerated study treatment. During the DLT evaluation period, none of the 15 patients developed any grade 4 toxicities or treatment discontinuation that was related to agents investigated by this trial. The most frequent treatment-related adverse event was fever/chill (26.7%). Of the 18 patients, no patients achieved a partial or complete response, and the median progression-free survival for 18 patients was 1.1 months (95% CI, 1.0–1.3) and the results suggest no clinical benefit from this treatment. Ad5CRT’s circulating virus half-life was approximately 10 min. Maximum tolerated dose was 2 × 1012 virus particles. Single-dose intravenous Ad5CRT was feasible and well tolerated in patients with gastrointestinal cancer liver metastasis. Ad5CRT did not provide meaningful clinical benefit, and the reason for the lack of efficacy was not entirely clear because no pharmocodynamic assessment was made.

Background and objectives Additional surgery should be done after non-curative endoscopic resection (ER) in early gastric cancer (EGC) due to the risk of lymph node metastasis (LNM). However, the distribution pattern of LNM in these patients is complicated and unpredictable. The aim of this study is to identify any different distribution patterns of LNM in patients with EGC who underwent additional surgery after non-curative (ER) comparing to those without ER. Methods Patients who underwent surgery for EGC between 2001 and 2016 were included. Enrolled patients were divided into two groups, those who underwent additional surgery after non-curative ER and those who underwent direct surgery without a history of ER. Demographics, tumor characteristics and LNM distribution pattern were analyzed. Results Among 4295 patients with EGC, 404 patients had a history of preoperative ER, and 3891 patients did not. After the application of exclusion criteria, 23 (7.1%) of 322 patients undergoing additional surgery had LNM. The additional surgery group showed less LNM, fewer nodal stations and more restricted distribution pattern of LNM. Conclusions The distribution pattern of LNM in EGC is complicated. However, more restricted locoregional LNM could be expected in cases of additional surgery after non-curative ER than after direct surgery.

Background Discrepancies in the clinicopathologic parameters pre- and post-endoscopic submucosal dissection (ESD) sometimes necessitate additional surgical resection. The aim of this study was to assess such discrepancies in clinicopathologic parameters before and after ESD in the context of reducing the risk of failure of curative ESD. Methods Data on 712 early gastric cancer patients were prospectively collected from 12 university hospitals nationwide. The inclusion criteria were differentiated carcinoma

Early gastric cancers (EGCs) within the mucosal layer of the gastric wall have a small risk of lymph node (LN) metastasis. We reviewed clinicopathology data for patients who underwent surgery for EGC between 2001 and 2013 at the National Cancer Center, Korea. Poisson regression analyses were performed to compare the risk of LN metastasis according to the depth of tumor invasion in patients with mucosal EGCs. Among the 1776 EGC patients included, 580 (32.7 %) had tumors confined to the lamina propria (LP; LP group) and 1196 (67.3 %) had tumors invading the muscularis mucosae (MM; MM group). Seventy-one patients (4.0 %) had LN metastasis, and the MM group had a significantly higher rate of LN metastasis (59 patients, 4.9 %) than the LP group (12 patients, 2.1 %; P = 0.004). A multivariate analysis showed that tumors invading the MM (adjusted risk ratio 1.95; P = 0.045) were significantly associated with LN metastasis in addition to well-known risk factors, including tumor size greater than 3 cm, presence of ulceration, undifferentiated histologic type, and lymphovascular invasion. The incidence of LN metastasis was 1.87 % (95 % confidence interval 0.23–6.59 %) within tumors invading the MM that met the expanded criterion for endoscopic resection of differentiated histologic type of size 3 cm or smaller with ulceration. LN metastasis was not found in tumors meeting the absolute criteria for endoscopic resection. EGCs invading the MM had a higher rate of lymph node metastasis than those confined to the LP. Further study is needed to evaluate whether different curative treatment criteria are needed for LP-confined and MM-invading EGCs.

The effects of obesity on prognosis in gastric cancer are controversial. To evaluate the association between body mass index (BMI) and mortality in patients with gastric cancer. A single-institution cohort of 7765 patients with gastric cancer undergoing curative gastrectomy between October 2000 and June 2016 was categorized into six groups based on BMI: underweight (

Kaplan-Meier disease-free survival curves according to total number of lymph nodes examined (â ¤ 30, 31-45, >â 45) for all patients and for each stage subgroup. (A) All patients; (B) stage IA; (C) stage IB; (D) stage IIA; (E) stage IIB; (F) stage IIIA; (G) stage IIIB; (H) stage IIIC. (DOCX 327 kb)

Supplemental Material for Association of current Helicobacter pylori infection and metabolic factors with gastric cancer in 35,519 subjects: A cross-sectional study by Su Youn Nam, Bum Joon Park, Ji Hyung Nam, Kum Hei Ryu, Myeong-Cherl Kook, Jeongseon Kim and Won Kee Lee in United European Gastroenterology Journal

Kaplan-Meier overall survival curves according to total number of lymph nodes examined (â ¤ 30, 31-45, >45) for all patients and for each stage subgroup. (A) All patients; (B) stage IA; (C) stage IB; (D) stage IIA; (E) stage IIB; (F) stage IIIA; (G) stage IIIB; (H) stage IIIC. (DOCX 698 kb)

Univariate and Multivariate Analysis of Clinicopathologic Factors Associated with Overall Survival. (DOCX 42 kb)

A small differentiated gastric cancer with minute submucosal invasion after endoscopic resection is regarded as the curative resection criterion of an expanded indication. However, recent studies have shown a high incidence of lymph node metastasis in those meeting the expanded criteria. The aim of this study was to evaluate the validity of the 500 μm criterion and to determine an optimal cutoff value for the expanded indication. We reviewed the clinicopathological data of 1,322 patients who underwent curative resection for submucosal gastric cancer between 2001 and 2013. The full thickness of the submucosa and the incidence of lymph node metastasis according to the depth of the submucosal invasion were evaluated. The sensitivity, specificity, and positive and negative predictive values were calculated with receiver operating characteristic (ROC) curve analysis. The mean full thickness of the submucosa was 2,605 ± 1,760 μm, and the incidence of lymph node metastasis in 103 tumors meeting the expanded indication was 3.9 % (4/103). In the ROC analysis, the area under the curve was 0.664 (95 % confidence interval 0.538–0.791; p = 0.017), and the highest negative predictive value of 98 % was observed when the cutoff value was 300 μm. This study suggests that a range reduction in the depth of submucosal invasion is required to obtain a high negative predictive value. Further large-scale studies are required to validate the optimal cutoff value proposed in this study.

AIMS Intestinal metaplasia and atrophy of the gastric mucosa are associated with Helicobacter pylori infection and are considered premalignant lesions. The updated Sydney system is used for these parameters, but experienced pathologists and consensus processes are required for interobserver agreement. We sought to determine the influence of the consensus process on the assessment of intestinal metaplasia and atrophy. METHODS AND RESULTS Two study sets were used: consensus and validation. The consensus set was circulated and five gastrointestinal pathologists evaluated them independently using the updated Sydney system. The consensus of the definitions was then determined at the first consensus meeting. The same set was recirculated to determine the effect of the consensus. The second consensus meeting was held to standardise the grading criteria and the validation set was circulated to determine the influence. Two additional circulations were performed to assess the maintainance of consensus and intraobserver variability. Interobserver agreement of intestinal metaplasia and atrophy was improved through the consensus process (intestinal metaplasia: baseline κ = 0.52 versus final κ = 0.68, P = 0.006; atrophy: baseline κ = 0.19 versus final κ = 0.43, P

Although a number of feasibility studies for sentinel node (SN) concepts in gastric cancer have been conducted since 2000, there remains a debate regarding detailed detection techniques and oncological safety. Two important multicenter phase II clinical trials were performed in Japan that used different methods and reached different conclusions; one confirmed acceptable results with a false-negative rate of 7%, and the other showed an unacceptably high false-negative rate of 46.4%. The Sentinel Node Oriented Tailored Approach (SENORITA) trial is a multicenter randomized controlled phase III trial being performed in Korea. Patient enrollment is now complete and the long-term results are currently awaited. Recently, an image-guided SN mapping technique using infrared ray/fluorescence was introduced. This method might be a promising technology because it allows the clear visualization of SNs. With regard to the primary tumor, the non-exposed endoscopic wall-inversion surgery technique and non-exposure endolaparoscopic full-thickness resection with simple suturing technique have been reported. These methods prevent abdominal infection and tumor seeding and can be good alternatives to conventional laparoscopic gastric wedge resection. For indications, SN navigation surgery can be extended to patients who underwent non-curative endoscopic resection. Although a few studies have been performed on these patients, sentinel concepts may be beneficial to patients as they omit the need for additional gastrectomy. SN navigation surgery can lead to actual organ-preserving surgery and plays a key role in improving the quality of life of patients with early gastric cancer in the future.

BACKGROUND/AIMS Galectin-9 (Gal-9) is a member of the β-galactoside-binding lectin family. Our previous study revealed that Gal-9 suppresses migration, invasion, and epithelial-mesenchymal transition in gastric cancer cells. Gal-9 was reported to have anti-metastatic activity in patients with malignant melanoma, breast cancer, and hepatocellular carcinoma. Therefore, we aimed to evaluate the prognostic significance of Gal-9 in patients with gastric cancer. MATERIALS AND METHODS The clinical significance of Gal-9 was explored using clinical and pathological data from 619 patients with gastric cancer who underwent gastrectomy at National Cancer Center, Korea. Tissue microarray and immunohistochemical analyses were used to evaluate Gal-9 expression. The median follow-up duration was 65.7 months (range 0-79 months). Kaplan-Meier method was used to evaluate survival. Log-rank test was used to assess the differences in survival. RESULTS Based on the tumoral expression of Gal-9, 619 patients with gastric cancer were classified into two groups: Gal-9-positive patients (327, 52.8%) and Gal-9-negative patients (292, 47.2%). The Gal-9-positive group had a significantly lower overall (p=0.001, by log-rank test) and gastric cancer-specific mortalities (p

Purpose Recently, non-exposure simple suturing endoscopic full-thickness resection (NESS-EFTR) was developed to prevent tumor exposure to the peritoneal cavity. This study aimed to evaluate the feasibility of NESS-EFTR with sentinel basin dissection for early gastric cancer (EGC). Materials and methods This was the prospective SENORITA 3 pilot. From July 2017 to January 2018, 20 patients with EGC smaller than 3 cm without an absolute indication for endoscopic submucosal dissection were enrolled. The sentinel basin was detected using Tc99m-phytate and indocyanine green, and the NESS-EFTR procedure was performed when all sentinel basin nodes were tumor-free on frozen pathologic examination. We evaluated the complete resection and intraoperative perforation rates as well as the incidence of postoperative complications. Results Among the 20 enrolled patients, one dropped out due to large tumor size, while another underwent conventional laparoscopic gastrectomy due to metastatic sentinel lymph nodes. All NESS-EFTR procedures were performed in 17 of the 18 other patients (94.4%) without conversion, and the complete resection rate was 83.3% (15/18). The intraoperative perforation rate was 27.8% (5/18), and endoscopic clipping or laparoscopic suturing or stapling was performed at the perforation site. There was one case of postoperative complications treated with endoscopic clipping; the others were discharged without any event. Conclusions NESS-EFTR with sentinel basin dissection is a technically challenging procedure that obtains safe margins, prevents intraoperative perforation, and may be a treatment option for EGC after additional experience. Trial registration ClinicalTrials.gov Identifier: NCT03216174.

Background Worldwide, gastric cancer (GC) is the fourth most common malignancy and the most common cancer in East Asia. Development of targeted therapies for this disease has focused on a few known oncogenes but has had limited effects. Objective To determine oncogenic mechanisms and novel therapeutic targets specific for GC by identifying commonly dysregulated genes from the tumours of both Asian-Pacific and Caucasian patients. Methods We generated transcriptomic profiles of 22 Caucasian GC tumours and their matched non-cancerous samples and performed an integrative analysis across different GC gene expression datasets. We examined the inhibition of commonly overexpressed oncogenes and their constituent signalling pathways by RNAi and/or pharmacological inhibition. Results Hepatocyte nuclear factor-4α (HNF4α) upregulation was a key signalling event in gastric tumours from both Caucasian and Asian patients, and HNF4α antagonism was antineoplastic. Perturbation experiments in GC tumour cell lines and xenograft models further demonstrated that HNF4α is downregulated by AMPKα signalling and the AMPK agonist metformin; blockade of HNF4α activity resulted in cyclin downregulation, cell cycle arrest and tumour growth inhibition. HNF4α also regulated WNT signalling through its target gene WNT5A, a potential prognostic marker of diffuse type gastric tumours. Conclusions Our results indicate that HNF4α is a targetable oncoprotein in GC, is regulated by AMPK signalling through AMPKα and resides upstream of WNT signalling. HNF4α may regulate ‘metabolic switch’ characteristic of a general malignant phenotype and its target WNT5A has potential prognostic values. The AMPKα-HNF4α-WNT5A signalling cascade represents a potentially targetable pathway for drug development.

The possibility of lymph node metastasis is critical to the assessment of the indication for endoscopic submucosal dissection. The differentiation of tumors is an important predicting factor for lymph node metastasis. Even though gastric cancers frequently show intratumoral heterogeneity, most studies have not considered the effects of the minor histologic components. The purpose of this study was to investigate the relationship between the presence of undifferentiated type histology (UD-min) within differentiated type tumors and lymph node metastases in early gastric cancer confined to the mucosal layer.A retrospective study of 847 patients who underwent surgery for differentiated early gastric cancer, confined to mucosa, was conducted. We analyzed the proportion of the undifferentiated type components of the tumor and their relationship with lymph node metastasis.The overall rate of lymph node metastasis was 1.7 % (14/847 patients) and 215 differentiated tumors (25.4 %) have UD-min. UD-min was associated with female sex, younger age, larger tumor size, and the presence of ulcer. Lymph node metastasis rate with or without UD-min was 5.1 % (11/215) versus 0.5 % (3/632), respectively (p0.001). UD-min was found to be associated with lymph node metastasis in the multivariate analyses (odds ratio [OR] = 4.39, CI 1.08-17.89). When three risk factors (tumor size2 cm, ulcer, and UD-min) were present concurrently, the rate of lymph node metastasis was high (10 %).The presence of an UD-min component should be considered when assessing curative resection status of endoscopic submucosal dissection for differentiated type mucosal cancer.

Background and Aims The definition and incidence of gastric cancer (GC) without Helicobacter pylori (Hp) infection varies between studies. The aim of our study was to compare the characteristics of GC according to Hp infection status. Methods We evaluated the presence of Hp infection in 1833 GC patients with rapid urease tests, serology examinations, and histological evaluations. GC was classified as GC with current Hp infection (HpC-GC), GC with past Hp infection (HpP-GC), and GC not associated with Hp infection (HpN-GC). HpP-GC was defined as GC without current infection but with a positive serology test, glandular atrophy, and/or intestinal metaplasia. HpN-GC was defined as GC with negative Hp test results and no histological changes. Results The numbers of HpC-GC, HpP-GC, and HpN-GC were 1378 (75.2%), 412 (22.5%), and 43 (2.3%), respectively. Among GCs without current infection, 90.5% (412/455) were associated with HpP-GC. HpP-GCs were more common in older and male patients, had an increased incidence of synchronous cancer, and less frequently had a diffuse-type histology than HpC-GCs. HpN-GCs were more common in younger, female patients; had a higher proportion of diffuse-type cancers; and more frequently showed distant metastasis than HpP-GCs. In the 40s, the proportion of HpP-GCs with diffuse-type histology (41.9%) was lower than that of HpC-GCs (60.3%) (P = 0.016). The difference was also significant in the 50s (29.1% vs 40.1%, respectively, P = 0.004). Conclusions Most GCs in Korea without current Hp infection showed evidence of past Hp infection. The proportion of GCs with diffuse-type histology decreased in patients with past infection.

The importance of PPARγ (peroxisome proliferator-activated receptor γ) in gastric cancer (GC) is unclear. We investigated the role of PPARγ in GC cell lines and an animal model, and its prognostic significance of PPARγ in GC patients. We controlled PPARγ and galectin-9 expression by using siRNAs and lentiviral constructs. Interaction between PPARγ and galectin-9 was evaluated using luciferase and chromatin immunoprecipitation assays. PPARγ expression in GCs was determined by immunohistochemical staining of tissue microarrays and survival analysis was done. Overexpression of PPARγ was accompanied by increased galectin-9. Enhanced PPARγ or galectin-9 expression increased E-cadherin expression; decreased expression of N-cadherin, fibronectin, snail, twist and slug and reduced cell invasion and migration. PPARγ bound to the galectin-9 promoter region. Galectin-9 activity increased in PPARγ-overexpressing cells but decreased in PPARγ siRNA-treated cells. In a zebrafish xenograft model, the number of migrated cancer cells and number of fish with AGS cells in the tail vein were reduced in PPARγ-overexpressing GC cells. PPARγ was expressed in 462 of the 688 patients (69.2%) with GC. In 306 patients with intestinal-type GC, those with PPARγ-positive tumors had lower overall and cancer-specific mortalities than those with PPARγ-negative tumors. PPARγ expression was an independent prognostic factor for overall and GC-specific mortality in patients with intestinal-type GC (adjusted hazard ratio, 0.42; 95% CI, 0.22-0.81). PPARγ inhibits cell invasion, migration and epithelial-mesenchymal transition through upregulation of galectin-9 in vitro and in vivo.

The translation of high-throughput gene expression data into biologically meaningful information remains a bottleneck. We developed a novel computational algorithm, PATHOME, for detecting differentially expressed biological pathways. This algorithm employs straightforward statistical tests to evaluate the significance of differential expression patterns along subpathways. Applying it to gene expression data sets of gastric cancer (GC), we compared its performance with those of other leading programs. Based on a literature-driven reference set, PATHOME showed greater consistency in identifying known cancer-related pathways. For the WNT pathway uniquely identified by PATHOME, we validated its involvement in gastric carcinogenesis through experimental perturbation of both cell lines and animal models. We identified HNF4α-WNT5A regulation in the cross-talk between the AMPK metabolic pathway and the WNT signaling pathway, and further identified WNT5A as a potential therapeutic target for GC. We have demonstrated PATHOME to be a powerful tool, with improved sensitivity for identifying disease-related dysregulated pathways.

Background and Aims The effect of Helicobacter pylori eradication on de novo gastric cancer is controversial, although meta-analyses suggest a reduction in gastric cancer after eradication. The effect of high-density lipoprotein (HDL) on gastric cancer has been rarely reported. Methods In this large retrospective cohort study, participants underwent endoscopy and H pylori testing from 2003 to 2011 and underwent follow-up endoscopy and H pylori testing until 2013. H pylori infection was detected using a rapid urease test or histologic test. The H pylori eradication group was defined as successful eradication, whereas the H pylori persistent group was defined as noneradication or eradication failure. The risk of cancer was measured with hazard ratios (HRs) and 95% confidence intervals (CIs). Results Among 10,328 healthy subjects (5951 men; mean age, 48.7 years), 31 gastric cancers were detected during a median follow-up of 5.5 years. De novo gastric cancer developed in 21 of 3508 subjects (.6%) in the noneradication group, 4 of 2050 subjects (.2%) in the successful eradication group, and 6 of 4770 participants (.13%) in the absence of H pylori group. In the adjusted analysis, H pylori eradication decreased de novo gastric cancer risk (HR, .29; 95% CI, .10-.86) compared with the persistent group. The risk of de novo gastric cancer in absence of H pylori was also much lower compared with the persistent group (HR, .24; 95% CI, .09-.60). Low serum HDL increased the risk of de novo gastric cancer (HR, 2.67; 95% CI, 1.14-6.16). Conclusions Successful H pylori eradication reduced de novo gastric cancer, whereas low HDL increased its risk.

Radiation-induced hemorrhagic gastroduodenal vascular ectasia (GDVE) is rare but difficult to manage. Argon plasma coagulation (APC) has not yet been evaluated in the treatment of radiation-induced hemorrhagic GDVE. The efficacy of APC in patients with radiation-induced hemorrhagic GDVE has been investigated in this article.Eighteen patients with upper gastrointestinal (GI) bleeding caused by radiation-induced GDVE, including 13 with hepatocellular carcinoma, 3 with pancreatic cancer, and 2 with cholangiocarcinoma, were treated with APC. The efficacy of APC was retrospectively evaluated, based on cessation of macroscopic GI bleeding, resolution or stabilization of anemia and transfusion dependence, endoscopic ablation of almost all vascular lesions, complications, and recurrence.Mean patient age was 59 years (range 42-80 years). The median time from radiation to GDVE diagnosis was 4.6 months (range 3.3-21.5 months). The median number of APC sessions per patient was 2.4 (range 1-4). All 18 patients showed an endoscopic response to APC treatment, with sustained increases in mean hemoglobin level, from 6.6 g/dL (range 2.9-9.5 g/dL) to 9.7 g/dL (range 7.1-12.7 g/dL) (p0.001), and decreased dependence on transfusion, from 9.1 (range 0-30) to 4.1 (range 0-15) units of packed red blood cells per patient (p = 0.038) after last endoscopic eradication by APC treatment. There were no major procedure-related adverse events or deaths. At a median follow up of 4.7 months (range 0.6-24.5 months), none of the patients experienced recurrence of GDVE.APC showed short-term effectiveness and safety in the treatment of radiation-induced hemorrhagic GDVE.

BACKGROUND Prognosis of alpha-fetoprotein positive gastric cancer (AFPP-GC) remains elusive so far due to disparities in cohort size and baseline characteristics in previous studies. A propensity score matching (PSM) analysis as well as multivariable model was performed for unbiased evaluation of the outcome in AFPGC. METHODS Among 3034 gastric cancer patients who underwent curative gastric cancer surgery (R0, M0) at the National Cancer Center, Korea between 2002 and 2007, we identified 97 patients being positive for AFP either by elevation of serum-AFP levels >10 μg/L or by immunohistochemical staining. Due to marked disparities in baseline characteristics and cohort size, propensity-score-matching was performed which matched 87 AFPP-GC patients to the same number of AFP-negative gastric cancer (AFPN-GC) patients. Baseline characteristics were compared using χ2-test. Survival curves were compared using the Kaplan-Meier-method and multivariable regression analysis was performed to evaluate the effect of AFP-positivity while adjusting the effects of confounding variables. RESULTS AFPP-GC and AFPN-GC patients revealed marked disparities in patient cohorts. After PSM, groups were balanced for age, sex, tumor size, BMI, tumor location, grade of differentiation, presence of lymphatic vessel infiltration (LVI), Lauren histologic type and stage distribution. In multivariable regression analysis of the PSM-groups, only AFP-positivity and pathologic stage were predictive for overall survival (HR 2.98, CI 95% {1.7-5.1}, p

Several retrospective analyses on patients who underwent gastric cancer (GC) surgery revealed different survival outcomes between Eastern (Korean, Japanese) and Western (USA, Europe) countries due to potential ethnical and biological differences. This study investigates treatment outcomes between specialized institution for GC in Korea and Germany. The prospectively documented databases of the Gastric Cancer Center of the National Cancer Center, Korea (NCCK) and the Department of Surgery of the Technische Universitaet Muenchen (TUM), Germany were screened for patients who underwent primary surgical resection for GC between 2002 and 2008. Baseline characteristics were compared using χ2 testing, and 2 cohorts were matched using a propensity score matching (PSM) method. Patients’ survival was estimated using Kaplan–Meier method, and multivariable Cox proportional hazard model was used for comparison. Three thousand seven hundred ninety-five patients were included in the final analysis, 3542 from Korea and 253 from Germany. Baseline characteristics revealed statistically significant differences for age, tumor location, pT stage, grading, lymphatic vessel infiltration (LVI), comorbidities, number of dissected lymph nodes (LN), postoperative complications, lymph-node ratio stage, and application of adjuvant chemotherapy. After PSM, 171 patients in TUM were matched to NCCK patients, and baseline characteristics for both cohorts were well balanced. Patients in Korea had significantly longer survival than those in Germany both before and after PSM. When the analysis was performed for each UICC stage separately, same trend was found over all UICC stages before PSM. However, significant difference in survival was observed only for UICC I after PSM. This analysis demonstrates different survival outcomes after surgical treatment of GC on different continents in specialized centers after balancing of baseline characteristics by PSM.

Purpose As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea. Materials and Methods We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters. Results Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p

Purpose: The aim of the present study was to assess the association between the pre-operative plasma fibrinogen level and the adjacent organ involvement in advanced gastric cancer. Materials and Methods: A total of 923 pre-operative plasma samples were obtained from 923 patients diagnosed clinically as having advanced gastric cancer, and fibrinogen levels were measured by immunoassay. Associations between fibrinogen levels and clinicopathologic findings (depth of tumor, adjacent organ involvement, and lymph node metastasis), along with survival were examined by univariate and multivariate analyses. Results: Tumor size, tumor depth, and the presence of lymph node metastasis were found to be positively correlated with the preoperative plasma fibrinogen levels (P

Few results regarding the long-term survival from laparoscopy-assisted total gastrectomy (LATG) have been reported. The purpose of this study was to investigate the feasibility of LATG in terms of long-term survival and morbidity. A case–control study was conducted on 100 cases of LATG and 348 cases of open total gastrectomy (OTG) performed for treating clinical stage I (cT1N0, cT1N1, and cT2N0) gastric cancer from August 2003 to December 2008 at the National Cancer Center of Korea. The clinicopathological characteristics, surgical outcomes, and complications were compared between the LATG and OTG groups. The overall survival rate and disease-free survival rate were analyzed using a Cox proportional hazards model for multivariate analysis. The rate of postoperative complications was 27 %, the most common being anastomotic stenosis from LATG (9 %). There were no significant differences in surgical outcomes and complications between the LATG and OTG groups except for a longer operating time for LATG. Survival rates were also similar between groups; the hazard ratio of LATG versus OTG was 0.43 (95 % confidence interval [CI] = 0.15–1.20; p = 0.107) for overall survival and 0.47 (95 % CI = 0.19–1.18; p = 0.106) for disease-free survival. LATG may be a feasible procedure with acceptable complications and long-term survival rate for clinical stage I gastric cancer.

Focal CpG island hypermethylation and diffuse genomic hypomethylation signify the changes in the DNA methylation status in cancer cells. ALU and LINE-1 repetitive DNA elements comprise ~28% of the human genome. PCR-based measurements of these repetitive DNA elements can be used as a surrogate marker of the genomewide methylation content. Our study aimed to identify the timing of ALU and LINE-1 hypomethylations during multistep gastric carcinogenesis and their prognostic implications in gastric cancer (GC). In our study, we analyzed the methylation statuses of ALU and LINE-1 in 249 cases of gastric biopsy samples and another independent set of 198 cases of advanced GC by pyrosequencing. Regardless of the Helicobacter pylori infection status, a significant decrease in the ALU methylation levels was noted during the transitions from chronic gastritis to intestinal metaplasia and from gastric adenoma to GC. LINE-1 methylation decreased during the transition from intestinal metaplasia to gastric adenoma and no further decrease occurred during the transition from gastric adenoma to GC. A low LINE-1 methylation status was strongly associated with poor prognosis in GC. A multivariate analysis revealed that LINE-1 methylation status was an independent prognostic factor. Our findings suggest that ALU and LINE-1 hypomethylations are early events during multistep gastric carcinogenesis. Furthermore, the LINE-1 methylation status can be used as a molecular biomarker to define a subset of GC patients with poor prognosis.

Background The purpose of this study was to compare the clinical usefulness of the seventh Union Internationale Contre le Cancer/American Joint Committee on Cancer (AJCC/UICC) staging system vs the sixth AJCC/UICC staging system in patients with gastric cancer. Study Design Included were 1,799 patients who underwent surgery for gastric cancer between January 2001 and June 2005 at the National Cancer Center (South Korea). For the sixth and seventh AJCC/UICC staging systems, survival outcomes stratified by stage, by T classification, and by N classification were summarized using Kaplan-Meier curves and compared statistically using a log rank test; survival differences were quantified using hazard ratios estimated from a Cox regression model. The 2 systems were compared in terms of prognostic performances using the linear trend chi-square test, likelihood ratio chi-square test, and Akaike information criterion (AIC) in the Cox regression analysis. Results Significant survival differences between each stage were not found using the seventh staging system, especially for stages IB, IIA, and IIB (p = 0.14 and p=0.11). The sixth staging system had higher linear trend chi-square score and likelihood ratio chi-square score, which means better discriminatory ability, monotonicity, and homogeneity, and had smaller AIC, which indicates better optimistic prognostic stratification, especially in the N classification. The modified staging system combining the T classification of the seventh AJCC/UICC system and the N classification of the sixth system showed better prognostic performance compared with each separate version (sixth or seventh) of the staging system. Conclusions The seventh AJCC/UICC staging system is not more clinically useful than the sixth system in surgically treated patients with gastric cancer because of an inappropriate N classification. A new TNM system is required with a different N classification.

Background: Sentinel node biopsies (SNBs) have been clinically applied in melanoma and breast cancer for limited lymphadenectomy. However, the use of SNB remains controversial in gastric cancer due to unsatisfactory sensitivity and variability. This meta-analysis was performed to determine the sensitivity of SNB in gastric cancer and to identify factors that improve its sensitivity. Methods Feasibility studies on SNB in gastric cancer were searched for from 2001 to 2009 in Pubmed, Cochrane, and Embase. Forty-six reports, which included 2,684 patients, were found. Estimated sensitivities, detection rates, and negative (NPV), and positive predictive values (PPV) were calculated using a random effects model. Inter-study heterogeneity, meta-regression, and subgroup analysis for sensitivity was performed. Results The estimated sensitivity, detection rate, NPV, and PPV were 87.8%, 97.5%, 91.8%, and 38.0%, respectively, with significant inter-study heterogeneity (P

Background and Aim: Helicobacter pylori infection is a risk factor for gastric cancer. We evaluated whether H. pylori infection and premalignant histological changes are more prevalent in siblings of young gastric cancer patients. Methods: Young (age ≤ 40) gastric cancer patients (n = 185), their young siblings (n = 130), and young control participants (n = 287) were recruited. H. pylori infection and histological changes were assessed using the updated Sydney system in biopsy specimens from three regions. We analyzed the association of H. pylori infection and histological changes with gastric cancer using logistic regression analysis. Results: The H. pylori infection rate was significantly higher in young cancer patients than their siblings (odds ratio [OR] = 2.42, P = 0.001) or control participants (OR = 3.60, P

Background & Aims Two major types of gastric cancer, intestinal and diffuse, develop through distinct mechanisms; the diffuse type is considered to be more influenced by genetic factors, although the mechanism is unknown. Our previous genome-wide association study associated 3 single nucleotide polymorphisms (SNPs) with diffuse-type gastric cancer (DGC); 1 was a functional SNP (rs2294008) in prostate stem cell antigen ( PSCA ), but the loci of the other 2 were not investigated. Methods We performed high-density mapping to explore a linkage disequilibrium status of the 2 SNPs at chromosome 1q22. A DGC case-control study was conducted using DNA from 606 cases and 1264 controls (all Japanese individuals) and validated using DNA from Japanese (304 cases, 1465 controls) and Korean (452 cases, 372 controls) individuals. The effects of SNPs on function were analyzed by reporter assays and analyses of splice variants. Results A region of a strong linkage disequilibrium with the 2 SNPs contained mucin 1 ( MUC1 ) and other 4 genes and SNPs significantly associated with DGC (rs2070803: P = 4.33 × 10 −13 ; odds ratio [OR], 1.71 by meta-analysis of the studies on the 3 panels) but not with intestinal-type gastric cancer. Functional studies demonstrated that rs4072037 ( P = 1.43 × 10 −11 ; OR, 1.66 by meta-analysis) in MUC1 affects promoter activity and determines the major splicing variants of MUC1 in the gastric epithelium. Individuals that carry both SNPs rs2294008 in PSCA and rs4072037 in MUC1 have a high risk for developing DGC (OR, 8.38). Conclusions MUC1 is the second major DGC susceptibility gene identified. The SNPs rs2070803 and rs4072037 in MUC1 might be used to identify individuals at risk for this type of gastric cancer.

66 Background: In CLASSIC and MAGIC, MSI was a good prognostic factor, and adjuvant/perioperative chemotherapy had null/detrimental effect. Given the low prevalence of MSI in GCs and its association with other good prognostic variables, larger datasets are needed to draw more robust evidences on its specific prognostic/predictive impact. Methods: This was a multinational IPD meta-analysis of resectable GC pts enrolled in MAGIC, CLASSIC, ARTIST, ITACA-S. Data on pts’ demographics (age, sex, and race), primary site (stomach versus junctional), histotype (intestinal vs. other), T/N stage (7th TNM), treatment received (multimodal therapy vs. surgery alone) and MSI were pooled. Univariable and multivariable associations with disease-free survival (DFS)/overall survival (OS) were assessed. The predictive role of MSI according to treatment received was assessed overall and in the 2 RCTs with a surgery alone arm (MAGIC+CLASSIC). Results: We pooled 1,552 pts with available MSI status: 121 (7,8%) were MSI, 572 Caucasian/980 Asian. In MSI versus MSS subgroups, 5-y DFS was 71.8% (95% CI: 63.8-80.7%) versus 52.3% (49.6-55.0%) (HR = 0.50, 95% CI 0.35-0.72; p < 0.001); 5-y OS 77.4% (69.9-85.8%) versus 59.2% (56.6-62.0%) (HR = 0.50, 95% CI 0.34-0-74; p < 0.001). In multivariable analyses, MSI was independently associated with DFS (HR = 0.48 [0.33-0.70]; p < 0.001) and OS (HR = 0.48 [0.29-0.81]; p = 0.005), as T/N/race/treatment. Conclusions: In resectable primary GC, MSI is an independent good prognostic marker that should be adopted as stratification factor in future RCTs. Chemotherapy omission and/or immune checkpoint blockade should be prospectively investigated in MSI-high GCs according to the clinically-defined risk of relapse. [Table: see text]

Background: Although gastric cancer (GC) and duodenal ulcer (DU) are both strongly associated with Helicobacter pylori infection, a DU is negatively associated with the risk of GC. The aim of the study is to evaluate histologic risk factors for GC among patients with a DU. Materials and Methods: A total of 541 consecutive patients with GC were prospectively evaluated for the presence of a DU. Control patients with only a DU (n = 89) were recruited from health screening population. Histologic grading was assessed using the updated Sydney system for six gastric biopsies from three regions. GC risk among patients with a DU was evaluated using logistic regression analysis. Results: Among patients with GC, 7.6% (41/541) had a concomitant DU or an ulcer scar. Corpus-predominant/pangastritis were more frequently found in concomitant GC patients with a DU (90%) than in patients with a DU alone (62%) (p = .001). In patients with a DU, moderate–severe chronic inflammation at the lesser and greater curvatures of corpus was associated with GC risk (OR, 3.70; 95% CI, 1.46–9.36, and OR, 7.72; 95% CI, 3.18–18.7, respectively). Additionally, moderate–severe intestinal metaplasia (IM) at the antrum and corpus lesser curvature was associated with GC risk (OR, 7.52; 95% CI, 3.06–18.5, and OR, 9.25, 95% CI, 2.39–35.8, respectively). Conclusions: A DU is not rare in patients with GC in a high-risk region of GC. Patients with a DU with chronic corpus gastritis and IM have an increased risk of GC, thus those patients should be followed up for GC development.

While clinicians routinely follow up gastric cancer patients after curative resection to detect recurrence, the effectiveness of regular follow-up has not been proven, and no consensus has been reached regarding follow-up programs. Of the 1,767 patients who underwent curative resection for gastric cancer from 2001 to 2004, 310 (17.5%) developed recurrence during follow-up. The oncologic effectiveness of follow-up was evaluated using recurrence detection rates during follow-up and survivals. Clinicopathologic characteristics, the detection tools used, and times lapsed between recurrence and previous examinations were also investigated. Two hundred thirty-three (75.2%) of the 310 patients who developed recurrence were detected by regular follow-up (detected group). The frequencies of undifferentiated and diffuse-type recurrences were higher in patients with recurrence detected based on patient-initiated findings (undetected group) than in the detected group. Computed tomography and tumor markers were the first detection tools that yielded positive findings. Times between recurrence detection and previous examinations ranged from 2.8 to 5.3 months over the first 2 years. No difference in overall survival was found between the detected and undetected groups (log rank, P = 0.2). The oncologic effectiveness of regular follow-up after curative resection for gastric cancer was found to be unsatisfactory. A large-scale randomized controlled trial is required to identify the effectiveness of regular follow-up in terms of its oncologic, functional, psychological, and economical aspects.

Gastric carcinoma (GC) is one of the human cancers in which promoter CpG island hypermethylation is frequently found. We used the MethyLight assay to evaluate the methylation status of 16 CpG island loci that are hypermethylated in GC. We analyzed the relationship between CpG island hypermethylation of these 16 genes and the clinicopathological features in 191 advanced GCs. A significant difference was observed between the number of methylated genes in Epstein-Barr virus (EBV)-negative and microsatellite instability (MSI)-negative GCs of different histological types (Lauren classification; P

The aim of this study was to assess the prognostic significance of intraoperatively estimated surgical stage (sStage) as a complementary role for pathologic stage (pStage) in gastric cancer.This was a retrospective study of 1,543 patients who underwent curative resection for gastric cancer. Clinicopathologic and therapeutic factors, including sStage, were analyzed for prognostic significance. Prognosis was stratified by sStage and pStage, and the prognoses of patients with an overestimated sStage were compared with those with a nonoverestimated sStage in the same pStage.Overall accuracy of sStage versus pStage was 39% (T stage, 73.0%; N stage, 43.5%). Survival curves were obviously stratified by sStage and pStage: Ia (97.5% versus 97.9%), Ib (94.3% versus 92.4%), II (89.6% versus 84.2%), IIIa (74.2% versus 69.3%), IIIb (54.4% versus 50.4%), and IV (55.6% versus 36.7%), respectively (p0.001). In addition to pStage, age and sStage were found to be significantly associated with overall survival by univariate and multivariate analysis. In pStages II, IIIa, and IIIb, intraoperatively overestimated patients had significantly poorer survival than nonoverestimated patients.sStage should be considered as a complementary prognostic factor for pStage in gastric cancer after curative resection, especially in stages II and III patients.

Background and Objective Only a few surgeons with much experience of laparoscopic surgery perform laparoscopy-assisted total gastrectomy (LATG), because of its technical difficulty and concern about subsequent complications. The aim of this study was to evaluate the technical feasibility and safety of LATG as compared with laparoscopy-assisted distal gastrectomy (LADG) in gastric cancer. Methods From January 2002 to December 2007, LADG was performed in 473 patients and LATG in 67 patients at the Korean National Cancer Center. Surgical procedures and short-term surgical outcomes of LATG were analyzed. Results D2 lymph node dissection was performed in 35 LATG (52.2%) cases and in 274 LADG (57.9%) cases (P = 0.378). Mean blood losses during operation were 156.8 ± 158.0 ml and 190.7 ± 176.2 ml, respectively (P = 0.114). The open conversion rate for LATG was higher than LADG without significance (4.3% vs. 1.7%, P = 0.153). Complications occurred in 18 LATG cases (26.9%) and 38 LADG cases (8.0%) (P

Background: Helicobacter pylori eradication is recommended in post-gastric cancer resection, but premalignant changes may prevent the detection of H. pylori. The aim of this study was to determine appropriate biopsy site for detecting H. pylori in gastric cancer patients. Materials and Methods: Consecutive patients (194) with gastric adenocarcinoma were prospectively enrolled. Helicobacter pylori was evaluated by serology, histology and rapid urease test. Biopsy sites included antrum lesser curvature, upper body lesser curvature (UBLC) and upper body greater curvature (UBGC). Two biopsy specimens were obtained from each site for histological examination. One additional specimen was obtained from UBGC for the rapid urease test. Results: The overall infection rate of H. pylori was 84.0% (95% CI 78.9–89.2). The sensitivity of histology for detecting H. pylori at various sites was: antrum (54.9%; 95% CI 45.7–63.9), UBLC (80.3%; 95% CI 72.2–87.0) and UBGC (95.1%; 95% CI 89.6–98.2). Specificities of all three biopsy sites were more than 95%. Sensitivity and specificity of the rapid urease test performed at UBGC were 96% and 100%, respectively. Sensitivities of histology decreased in correlation with increasing severity of atrophy and intestinal metaplasia (both P

Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38-1.89, P = 1.11 x 10(-9)). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r(2) = 0.995, D' = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56-2.33, P = 8.01 x 10(-11)). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.

BACKGROUND. The objective of the current study was to assess the staging accuracy and prognostic role of preoperative endoscopic ultrasound (EUS) and computed tomography (CT) in patients with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy. METHODS. Presurgical LAGC patients underwent EUS and CT before and after 3 cycles of neoadjuvant chemotherapy. Chemotherapy was comprised of docetaxel (at a dose of 36 mg/m2) and cisplatin (at a dose of 40 mg/m2) on Days 1 and 8 of a 3-week cycle. RESULTS. Forty patients were enrolled in the study. After chemotherapy, the accuracy of EUS and CT was found to be 47% and 57%, respectively for T classification (P = .22) and 39% and 37%, respectively for N classification (P > .99). The 3-year overall survival (OS) rate for patients downstaged with EUS for T and/or N classification was greater than that for nondownstaged patients (69% vs 41%; P = .05). The 2-year recurrence-free survival (RFS) rate was also better for the EUS-downstaged patients than for the nondownstaged patients (77% vs 47%; P = .04). On multivariate analysis, EUS downstaging was found to be correlated with OS (hazards ratio [HR] of 0.12; P = .04), and was correlated with RFS with borderline statistical significance (HR of 0.27; P = .07). The differences in OS and RFS between the patients downstaged with CT and those not downstaged were not found to be statistically significant. CONCLUSIONS. Restaging by EUS and CT after neoadjuvant chemotherapy in patients with LAGC was found to be inaccurate. However, T and/or N downstaging by EUS was found to be correlated with better OS and RFS. Thus, downstaging by EUS may be a useful clinical parameter with which to predict a better outcome for LAGC patients. Cancer 2008. © 2008 American Cancer Society.

Helicobacter pylori (H. pylori) eradication is strongly recommended for gastric cancer patients who undergo subtotal gastrectomy. The efficacy of proton pump inhibitor-based triple therapy for H. pylori eradication has not been adequately assessed in the gastric remnant. The aim of this study was to compare the efficacy of postoperative versus preoperative H. pylori eradication therapy.A total of 138 distal gastric cancer patients with H. pylori infection were randomized to receive either preoperative (preop, N = 68) or postoperative (postop, N = 70) proton pump inhibitor-based triple therapy for H. pylori eradication. The regimen consisted of rabeprazole 10 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily for 7 days. Eradication was assessed by rapid urease test and histology 12 wk after surgery.By intention-to-treat (ITT) analysis, H. pylori eradication rates were 84.6% (95% CI 73.5-92.4) in the preop group and 83.1% (95% CI 71.7-91.2) in the postop group (P= 0.99). By per protocol (PP) analysis, the rates were 87.3% (95% CI 76.5-94.4) in the preop group and 86.9% (95% CI 75.8-94.2) in the postop group (P= 0.99). In the postop group, eradication rates did not differ with reconstruction method (Billroth I vs II, 80.4%[95% CI 66.1-90.6]vs 89.5%[95% CI 66.9-98.7] by ITT analysis (P= 0.49), and 85.7%[95% CI 71.5-94.6]vs 89.5% (95% CI 66.9-98.7) by PP analysis, P= 0.99).In distal gastric cancer patients, the effect of proton pump inhibitor-based triple therapy for H. pylori eradication was not different whether given postoperatively or preoperatively.