Clinicopathological Characteristics And Molecular Mechanisms Of Development In Gastric Stump Cancer

Background:Total gastrectomy is a widely accepted procedure for treating gastric stump cancer.However,subtotal gastrectomy would benefit elective patients with gastric stump cancer after distal gastrectomy for benign lesions.The aim of this study was to clarify the safety and long-term outcomes of subtotal gastrectomy in treating gastric stump cancer after distal gastrectomy for benign lesions.Methods:A total of 53 patients with gastric stump cancer located at the anastomotic site or gastric body between May 1999 and December 2018 at our hospital were included..In total,21 patients underwent subtotal gastrectomy,and the remaining 24 patients underwent total gastrectomy.Clinicopathological data,operative data,and overall survival were compared.Results:The operative duration,estimated blood loss volume,and length of hospital stay were similar between the subtotal gastrectomy and total gastrectomy groups.The postoperative complications were similar between the two groups,but no cases of anastomotic leakage were noted in the subtotal gastrectomy group.Total gastrectomy was associated with significantly more retrieved lymph nodes than subtotal gastrectomy(18.5 ± 11.5 vs.10.7±9.2;p=0.017),while the number of metastatic lymph nodes did not differ between the groups(2.9±3.5 vs.1.9±3.6;p=0.329).The median survival time in the subtotal gastrectomy group was 81.0 months(95%confidence interval(CI),68.906 to 93.094 months);which was similar to the 45.0 months(95%CI,15.920 to 74.080 months)observed in the total gastrectomy group(p=0.236).Both univariate and multivariate analyses showed that tumor location and histological type were prognostic factors,while surgery type was not a prognostic factor.Further stratified analyses according to tumor location revealed that overall survival was not significantly different between the two groups among patients with tumors located at the anastomotic site,while overall survival in the total gastrectomy group was significantly better than that in the subtotal gastrectomy group among patients with tumors located in the gastric body(p=0.046).Conclusions:The results of the current study indicate that subtotal gastrectomy is a suitable alternative surgical procedure for gastric stump cancer located at the anastomotic site after distal gastrectomy for benign lesions.The short-term outcomes and long-term prognoses of subtotal gastrectomy are comparable with those of total gastrectomy.Background:There is no study to investigate the influence of the interval time between the first gastric cancer surgery and the gastric stump cancer on the prognosis of gastric stump cancer.The study based on the influence of different interval time on the prognosis of gastric stump cancer may be helpful to distinguish recurrent cancer and new cancer of gastric stump.The aim of this study was to investigate the impact of the interval time between the first gastric cancer surgery and the occurrence of gastric stump cancer on the prognosis of gastric stump cancer,in order to distinguish gastric stump cancer with different biological characteristics of by the interval time.Methods:70 patients with gastric stump cancer after radical distal gastrectomy for cancer at our hospital from January 1999 to December 2018 were enrolled in this study.The patients were divided into two groups.The surv_cutpoint function of the R package survminer was used to determine the optimal cut-off values of interval time.According to the optimal cutoff value,the patients were divided into two groups.By comparing the clinicopathological characteristics and long-term survival rate of the two groups,the optimal cutoff value was identified as a prognostic factor.Results:The overall survival of patients with interval<4 years was significantly worse than that of patients with interval?4 years(P=0.007).There were no significant differences in demographic characteristics,clinicopathological data and surgical data between the two groups.According to the tumor location,it was found that when the tumor was located in the anastomotic stoma and remnant stomach body,the overall survival of patients with an interval?4 years was still significantly better than that of patients with an interval<4 years,and the difference was statistically significant.When the tumor was located in the cardia,there was no significant difference in overall survival between the two groups.Multivariate analysis showed that the interval<4 years,the depth of local invasion and lymphovascular invasion were independent factors for prognosis.Conclusion:In this study,we found that the prognosis of patients with gastric stump cancer after distal gastrectomy,with the interval between the first operation and the diagnosis of gastric stump cancer<4 years,was significantly worse than that of patients with the interval?4 years,which was an independent factor affecting the prognosis of patients.The prognosis of the two groups is different,which may indicate different biological behaviors.The prognosis of the patients<4 years is worse,which may be recurrent cancer or residual cancer of the remnant stomach.This study provides some clues for the differentiation of recurrent carcinoma of remnant stomach,gastric stump cancer and gastric multiple carcinoma.Background/Aims:The incidence of gastric stump cancer is increasing year by year.The resection rate of gastric stump cancer is low,and the prognosis is poor.It seriously threatens the life and health of patients.At present,the most important factor is duodenogastric reflux.Trypsin in duodenal fluid is a specific activator of protease activated receptor-2(PAR2),which is involved in the development of inflammation and many kinds of tumors,Our previous study showed that the positive rate of PAR2 in gastric stump carcinoma and paracancerous mucosa in Billroth ? group with obvious reflux was higher than that in Billroth ? group with mild reflux,indicating that PAR2 plays an important role in the development of gastric stump carcinoma.This study aims to confirm whether PAR2 activation is involved in the occurrence of gastric stump cancer,so as to clarify the molecular mechanism of gastric stump cancer,and provide scientific theoretical basis for the prevention and treatment of gastric stump cancer.Methods:C57BL/6 male mice were used to establish the model of duodenogastric reflux by gastrointestinal anastomosis,and the effect of duodenogastric reflux on gastric stump cancer was evaluated by comparing with the sham operation group and control group.After the establishment of duodenogastric reflux model in mice,we intervened with carcinogens MNU and GB88,a inhibitor of PAR2,and divided the mice into four groups.They were:MNU+GB88 group,MNU+control group,GB88 group and control group.After a certain period of time,the mice were killed to evaluate the gastrointestinal anastomotic lesions.We further investigated the function of PAR2 in gastric cancer cell lines AGS and BGC-823.Results:In the duodenogastric reflux model of mice,high-grade intraepithelial neoplasia occurred at the anastomotic site 4 months after operation,but no tumor was found in the control group and sham operation group.In the background of no carcinogen,after 14 months of intervention with GB88 or olive oil,it was found that the number of cancerous mice in the control group(8/11)was significantly more than that in the GB88 intervention group(2/10)(P=0.027).Under the intervention of MNU,the mice in the control group which were given olive oil after gastrointestinal anastomosis began to die 3 months after operation,while the mice in the GB88 intervention group did not.The mice were killed 4 months after operation,and the occurrence of tumor was found in the olive oil control group.PAR2 immunohistochemical staining was positive in all gastric stump carcinoma.We found that knockdown PAR2 significantly inhibited the proliferation,clone formation,stem cell molecular expression,invasion and migration of gastric cancer cell lines.Conclusion:Trypsin in duodenal fluid may activate PAR2 on the surface of gastric epithelial cells in gastrointestinal anastomotic stoma,thus promoting the formation of gastrointestinal anastomotic tumor.PAR2 plays an important role in the occurrence of gastric stump cancer.PAR-2 plays an important role in the proliferation,stem properties maintenance,invasion and migration of gastric cancer cell lines.