Both variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 ...polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans.
We genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer.
The IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction = 0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR 95% CI = 17.76 6.17-51.06) or the -592C (OR 95% CI = 8.37 2.79-25.16) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction = 0.080).
Inflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer.
Endoscopic resection (ER) is an effective treatment for early gastric cancer (EGC) without lymph node metastasis. However, after ER additional surgery may be needed to manage the risks presented by ...residual cancer or lymph node metastasis.
ER was performed on 344 gastric adenocarcinomas between November 2001 and April 2006 at the Korean National Cancer Center under the strict pre-procedural indication. The authors performed operations in 43 patients due to: residual mucosal cancer, a mucosal cancer larger than 3 cm, or a submucosal cancer regardless of size or margin involvement. ER and surgical specimens were reviewed and analyzed for residual cancer and lymph node metastasis.
Based on examinations of ER specimens, cancer was confined to the mucosal layer in 15 patients (34.9%) and invaded the submucosal layer in 28 patients (65.1%). Surgical specimens showed residual cancer in 17 patients (39.5%) and lymph node metastasis in four (9.3%). Neither residual cancer nor lymph node metastasis was found in patients with less than 500 microm submucosal invasion without margin involvement in ER specimens. In three of four patients with lymph node metastasis, the depth of submucosal invasion was 500 microm or more; the remaining patient had a 4-cm-sized differentiated mucosal cancer.
When a pathologic evaluation of an ER specimen reveals more than 500 microm of submucosal invasion or a mucosal cancer of larger than 3 cm, surgery should be considered due to the risk of lymph node metastasis.
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).
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 Tc
-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.
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.
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.
ClinicalTrials.gov Identifier: NCT03216174.
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.
Background
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.
Methods
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.
Results
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 (
p
< 0.001). 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 size >2 cm, ulcer, and UD-min) were present concurrently, the rate of lymph node metastasis was high (10 %).
Conclusions
The presence of an UD-min component should be considered when assessing curative resection status of endoscopic submucosal dissection for differentiated type mucosal cancer.
Early gastric cancer (EGC) can be treated by minimally invasive endoscopic resection and has an excellent prognosis. The aim of this study was to investigate whether repeated ...esophagogastroduodenoscopy (EGD) screening is an effective method for detecting EGC that can be treated by endoscopic resection.
For patients diagnosed with gastric cancer in the Korean National Cancer Center screening program, we analyzed the incidence of gastric cancer, clinicopathological characteristics, and treatment modality according to whether they had (repeated screening group) or not (infrequent screening group) undergone EGD screening within 2 years before diagnosis.
Of the 18,414 patients who underwent EGD, 81 (0.44%) were found to have gastric cancer. Incidence of gastric cancer in repeated screening group was lower than that of infrequent screening group (multiple adjusted odds ratio=0.45, 95% confidence interval: 0.26-0.77, P=0.004). The proportion of EGCs was 96% (25 of 26) n the repeated screening group and 71% (34 of 48) in the infrequent screening group (P=0.01). Mean (SD) tumor size was smaller 1.9 (1.2) vs. 3.0 (1.6) cm, P=0.01 and the proportion of intramucosal cancer was higher 81% (21 of 26) vs. 50% (24 of 48), P=0.02 in the former than in the latter. Endoscopic resection was performed more frequently in the repeated screening group 54% (14 of 26) vs. 23% (11 of 48), P=0.007.
Repeated endoscopic screening within 2 years decreased the incidence of gastric cancer and endoscopic resection could be applied to more patients who underwent EGD screening within 2 years.
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.
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.
What's new?
Activation of peroxisome proliferator‐activated receptor γ (PPARγ) is capable of undermining certain malignant properties of gastric cancer cells in vitro, suggesting that it may be of relevance in human gastric cancers. Here, in gastric cancer cell and zebrafish models, PPARγ overexpression inhibited epithelial‐mesenchymal transition and led to reductions in cell invasion and migration. The effects of PPARγ overexpression were associated with galectin‐9 upregulation. In human patients with intestinal‐type gastric cancer, positive PPARγ tumor status was linked to reduced overall and cancer‐specific mortalities. The findings suggest that PPARγ may be a therapeutic target and prognostic factor in gastric cancer.
Background
Endoscopic screening has been adopted in South Korea for the national screening of gastric cancer (GC). This study aimed to assess the effect on overall survival of GC patients and ...determine the optimal endoscopic screening interval.
Methods
The baseline characteristics and overall survival of GC patients treated at the National Cancer Center, Korea, between 2010 and 2016 were compared between those without a history of endoscopic evaluation (group N) and those in whom the interval between the last endoscopic evaluations and diagnosis of GC was ≤ 1, 1–2, 2–3, 3–4, or > 4 years (groups 1–5, respectively).
Results
A total of 2362 patients met the criteria for the study (1060 in group N and 1302 in groups 1–5). More patients in groups 1–5 were diagnosed with stage I GC (83.7, 83.7, 71.8, 78.2, and 71.6%, respectively) than in group N (62.4%,
P
< 0.001) and were treated endoscopically (38.8, 33.8, 24.7, 21.8, and 15.5%, respectively, vs. 13.5%;
P
< 0.001). Group 2 had less-advanced tumor stages (
P
= 0.001) and was more likely to have received endoscopic treatments (
P
= 0.026) than group 3. Hazard ratios for death were significantly lower in groups 2 (0.45; 95% confidence interval CI, 0.32–0.64) and 3 (0.57; 95% CI, 0.33–0.98) than in group N; the decrease was not significant in group 4 (0.49, 95% CI, 0.20–1.20).
Conclusions
Endoscopic screening every 3 years may reduce the mortality of GC patients, though screenings at least every 2 years may benefit patients with less-advanced stages.
PDF
