Comparisons between intestinal and diffuse gastric cancer in response to apatinib: Data from post-marketing phase IV study.

36 Background: Intestinal and diffuse gastric cancer are main histological types of gastric cancer, based on Lauren’s classification, which account for 34–47% and 46–57%, respectively. Patients (pts) with intestinal gastric cancer have better prognosis. The present study aimed to compare the safety and efficacy of apatinib between the two intestinal gastric cancer, based on data from post-marketing Phase IV study (Ahead-G201). Methods: The single-arm, open-label, multi-center, Phase IV trial enrolled advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction after failure of ≥2 lines of chemotherapy. Data of pts with intestinal and diffuse gastric cancer were collected and compared. Results: As of 2017/7/10, 96 intestinal and 104 diffuse pts were recruited. Differences in age (64 vs. 55 yrs), gender (male: 77.1% vs. 57.7%) and disease duration ( > 12 months: 71.3% vs. 56.7%) were detected. Between intestinal and diffuse gastric cancer, there was no discrepancy in incidences of adverse events (AEs) (78.1% vs. 73.1%) and Grade ≥3 AEs (41.7% vs. 38.5%). The incidences of typical AEs associated anti-angiogenesis drugs were also comparable (hypertension 26.0% vs. 16.4%; proteinuria 14.6% vs. 20.2%; hand-foot-skin reaction 16.7% vs. 9.6%). No statistical difference was observed in best overall response rate (12.8% vs. 14.3%) and disease control rate (76.0% vs. 64.3%). Survival benefit in pts with intestinal gastric cancer was detected (progression free survival: 5.52 vs. 2.76 months, p = 0.036; overall survival: 8.11 vs. 4.70 months, p = 0.047). However, the multivariable Cox regression model analysis showed that histological type was not independently prognostic factors for survival, indicating that clinical benefit of pts with intestinal gastric cancer was influenced by other factors. Conclusions: Compared with diffuse gastric cancer, pts intestinal gastric cancer have more clinical benefit after treated by apatinib. However, histological type based on the Lauren’s classification was not independently prognostic factors for survival, which needs to be further analyzed, considering the small sample size. Clinical trial information: NCT02426034.

Effect of a mixed type Lauren's classification on agressiveness and lymph node metastasis in early gastric cancer.

28 Background: The clinicopathological features of mixed type (MT) early gastric cancer (EGC) according to Lauren’s classification remain uninvestigated. This study aimed to clarify the clinicopathological features of MT EGC, particularly in relation to lymph node metastasis (LNM) and long-term survival. Methods: This study included 5,309 patients who underwent gastrectomy for EGC. The clinicopathological features, LNM, and long-term outcomes of patients with MT carcinomas were compared to those with intestinal type (IT) and diffuse type (DT) cancers. Furthermore, we evaluated the predictors of LNM in each Lauren classification subgroup. Results: Patients with MT carcinomas were more likely to have larger tumors, submucosal invasion, lymphovascular invasion (LVI), and LNM compared to those with IT or DT carcinomas. Multivariate logistic regression analysis revealed that Lauren’s classification was a significant predictor of LNM ( P < 0.001). The significant predictors of LNM in MT carcinomas were female sex, greater tumor size, presence of submucosal invasion, and LVI. However, the overall survival of patients with MT carcinoma was not significantly different from that of patients with IT or DT carcinomas ( P= 0.104). Conclusions: The presence of MT EGC carries a higher risk of LNM compared to IT or DT carcinomas. Therefore, MT carcinomas should be managed with gastrectomy that includes lymph node dissection instead of endoscopic resection.

Evaluation of the feasibility of expression microarray analysis in endoscopically obtained biopsies of gastric carcinoma and their clinical applicability

21164 Background: The feasibility of extracting high quality RNA for expression microarray analysis from endoscopic biopsy in gastric carcinoma has not been previously established. Methods: Patients with histologically confirmed locally advanced gastric or gastroesophageal junction adenocarcinoma were screened for enrollment in an NCI-sponsored trial of neoadjuvant irinotecan and cisplatin chemotherapy (NC1–5917). All patients underwent a repeat endoscopic biopsy for the procurement of fresh tumor tissue. Gross microdissection was performed to enrich the sample to at least 80% malignancy. RNA was isolated from the tumor specimens using RNeasy columns (Qiagen) and its quality verified by RNA 6000 NanoAssay and Bioanalyzer 2100 (Agilent). Gene expression profiling was performed on Human Genome U133A GeneChip (Affymetrix) which contained 22,215 oligonucleotide-base probe-sets. Differential gene expression profiles for Lauren's classification were assessed using empirical Bayes t test, a threshold p < 0.001 was considered statistically significant. Results: Of 36 patients with previous biopsy confirmed gastric cancer, repeat endoscopic biopsy identified carcinoma in 28 patients (78%, 95%CI 61–90%). Adequate RNA for microarray analysis was obtained from 21 patients-representing 58% of those who presented for the procedure and 75% in whom endoscopic biopsies confirmed malignancy. This yield improved with increasing number of samples taken. Lauren's classification was available on 26 patients who underwent resection. From the total 54,613 gene probe-sets on the arrays, comparison of the expression profiles of diffuse-type and intestinal-type identified 167 genes that were differentially expressed. Diffuse gastric cancer demonstrated altered expression of genes related to cell-matrix interaction whereas intestinal gastric cancer expression analysis showed enhancement of cell growth. Conclusions: Endoscopic biopsy for expression analysis of gastric cancer is feasible with increasing yield with each core taken. Expression analysis at the time of endoscopic biopsy can differentiate Lauren's histology, a characteristic not routinely evaluable by pathologic review. No significant financial relationships to disclose.

Prevalence of Helicobacter pylori infection in advanced gastric carcinoma

BACKGROUD: There is substantial evidence that infection with Helicobacter pylori plays a role in the development of gastric cancer and that it is rarely found in gastric biopsy of atrophic gastritis and gastric cancer. On advanced gastric tumors, the bacteria can be lost from the stomach. AIMS: To analyze the hypothesis that the prevalence of H.pylori in operated advanced gastric carcinomas and adjacent non-tumor tissues is high, comparing intestinal and diffuse tumors according to Lauren's classification METHODS: A prospective controlled study enrolled 56 patients from "Hospital Universitário", Federal University of Rio Grande do Norte, Natal, RN, Brazil, with advanced gastric cancer, treated from February 2000 to March 2003. Immediately after partial gastrectomy, the resected stomach was opened and several mucosal biopsy samples were taken from the gastric tumor and from the adjacent mucosa within 4 cm distance from the tumor margin. Tissue sections were stained with hematoxylin and eosin. Lauren's classification for gastric cancer was used, to analyse the prevalence of H. pylori in intestinal or diffuse carcinomas assessed by the urease rapid test, IgG by ELISA and Giemsa staining. H. pylori infected patients were treated with omeprazole, clarithromycin and amoxicillin for 7 days. Follow-up endoscopy and serology were performed 6 months after treatment to determine successful eradication of H. pylori in non-tumor tissue. Thereafter, follow-up endoscopies were scheduled annually. Chi-square and MacNemar tests with 0.05 significance were used. RESULTS: Thirty-four tumors (60.7%) were intestinal-type and 22 (39.3%) diffuse type carcinomas. In adjacent non-tumor gastric mucosa, chronic gastritis were found in 53 cases (94.6%) and atrophic mucosa in 36 patients (64.3%). All the patients with atrophic mucosa were H. pylori positive. When examined by Giemsa and urease test, H. pylori positive rate in tumor tissue of intestinal type carcinomas was higher than that in diffuse carcinomas. In tumor tissues, 34 (60.7%) H. pylori-positive in gastric carcinomas were detected by Giemsa method. H. pylori was observed in 30 of 56 cases (53.5%) in tissues 4 cm adjacent to tumors. This difference was not significant. Eradication of H. pylori in non-tumor tissue of gastric remnant led to a complete negativity on the 12th postoperative month CONCLUSIONS: The data confirmed the hypothesis of a high prevalence of H. pylori in tumor tissue of gastric advanced carcinomas and in adjacent non-tumor mucosa of operated stomachs. The presence of H. pylori was predominant in the intestinal-type carcinoma.