1.Improving a follow-up plan based on the tumor deposits status and recurrence pattern of stage Ⅱ/Ⅲ gastric cancer patients after radical gastrectomy
Kelei HUA ; Mingke HUO ; Zhichuang DONG ; Sen LI ; He ZHANG ; Yingkun REN ; Yi CAO
Chinese Journal of General Surgery 2024;39(10):783-789
		                        		
		                        			
		                        			Objective:To investigate the relationship between cancer node status identified after radical resection and patterns of recurrence in stage Ⅱ/Ⅲ gastric cancer patients for developing personalized follow-up plans in node-positive patients.Methods:A retrospective analysis was conducted on 706 stage Ⅱ/Ⅲ gastric cancer patients who underwent curative intent surgery at Henan Cancer Hospital from Sep 2015 to Sep 2018. Patients were categorized into node-positive (TDs +) and node-negative (TDs -) groups based on their cancer node status. Clinical-pathological characteristics and recurrence patterns were compared between the groups to formulate an optimized follow-up plan. Results:Among the patients, there were 112 TDs + and 594 TDs - cases. TDs - patients exhibited significantly better overall survival and disease-free survival rates at 1 and 3 years compared to the TDs + group (92.4%,72.2% vs. 79.4%,38.8%;87.9%,68.6% vs. 66.7%,35.9%, all P<0.05). The cumulative recurrence rates of peritoneal and distant metastases were higher in TDs + patients compared to TDs - patients, with statistical significance (33.0% vs. 14.5%,21.4% vs. 10.8%, χ 2=21.285,8.851 all P<0.05). TDs + patients experienced significantly earlier median time to distant metastasis compared to TDs - patients (9.0 months vs. 15.4 months , Z=-2.294 P=0.022). The risk of peritoneal metastasis recurrence was higher in the TDs + group, showing a bimodal recurrence pattern at 8.5 and 15.0 months post-surgery. TDs + patients also had a higher risk of distant metastasis recurrence, with a single peak at 6 months. Conclusion:Postoperative recurrence patterns differ between TDs + and TDs - patients, and an optimized follow-up plan can enhance early detection of recurrence.
		                        		
		                        		
		                        		
		                        	
2.The effect of neoadjuvant chemotherapy on the prognosis of resectable gastric neuroendocrine carcinoma
Kelei HUA ; Yingkun REN ; Mingke HUO ; Zhichuang DONG
Chinese Journal of General Surgery 2022;37(3):201-206
		                        		
		                        			
		                        			Objective:To investigate the effect of neoadjuvant chemotherapy on the prognosis of gastric neuroendocrine cancer.Methods:This study included 102 patients with gastric neuroendocrine cancer, the disease-free survival rate (DFS) and overall survival rate (OS) were compared between two groups according whether they were given neoadjuvant chemotherapy before radical resection.Results:Ninteen of the 102 patients received neoadjuvant chemotherapy combined with surgery, while the other 83 patients received upfront surgery . The 1-year survival rate of the direct operation group and the NAC group was 83.0% and 51.8%, respectively, and the 3-year survival rate was 63.0% and 33.3%, respectively ( χ2=9.182, P=0.002). The 1-year disease-free survival rate was 80.4% and 38.5%, respectively, and the 3-year disease-free survival rate was 59.8% and 25.7%, respectively ( χ2=11.142, P=0.001). Subgroup analysis showed that the difference between the two groups was mainly significant between MANEC patients ( χ2=10.742, P=0.001). Multivariate analysis showed that neoadjuvant therapy was an independent risk factor affecting the overall survival rate (all P<0.05). Univariate analysis shows that only adjuvant chemotherapy is the risk factor affecting disease-free survival ( P<0.05). When the neoadjuvant chemotherapy and the direct surgery were matched 1∶1, the OS and DFS of the direct surgery group were better than those of the NAC patients ( χ2=4.014, 3.954; P=0.045, 0.047). Conclusion:Neoadjuvant chemotherapy failed to improve the prognosis of patients with gastric neuroendocrine cancer/MANEC.
		                        		
		                        		
		                        		
		                        	
3.Expression of miR-128-3p in gastric cancer and its effect on migration and invasion of gastric cancer cells
Kelei HUA ; Yingkun REN ; Mingke HUO ; Zhichuang DONG
Chinese Journal of General Surgery 2022;37(4):279-283
		                        		
		                        			
		                        			Objective:To study the effects of miR-128-3p on the migration and invasion of the gastric cancer cells.Methods:qRT-PCR was used to detect the expression of miR-128-3p in 126 gastric cancer tissues and adjacent tissues from Jan 2014 to Jan 2016 at He'nan Cancer Hospital. The effect of miR-128-3p on the invasion and migration of gastric cancer cell line was detected.The expression of miR-128-3p related proteins was detected by Western blotting, miRNA on-line target prediction tool for the prediction of miR-128-3p directly regulated downstream target genes.Results:the expression of miR-128-3p in gastric cancer was significantly higher than that in adjacent non-tumor tissues ( P<0.05). The expression of miR-128-3p was correlated with the vascular tumor thrombus, pN staging and pTNM staging, the prognosis of patients with high expression of miR-128-3p was poor (all P<0.05). MiR-128-3p expression was significantly higher in gastric cancer cell lines ( P<0.05). Online target prediction tool and double luciferase reporter gene showed that CLDN18 was a downstream target gene directly regulated by mir-128-3p. Conclusion:The high expression of miR-128-3p is related to the poor prognosis of gastric cancer patients.
		                        		
		                        		
		                        		
		                        	
4.A Nomogram model involving preoperative inflammatory markers for predicting postoperative overall survival in patients with stage Ⅰ-Ⅲ gastric cancer
Kelei HUA ; Mingke HUO ; Zhichuang DONG ; Sen LI ; He ZHANG ; Yingkun REN
Chinese Journal of General Surgery 2022;37(10):749-754
		                        		
		                        			
		                        			Objective:To establish a nomogram to predict overall survival of patients with stage Ⅰ-Ⅲ gastric cancer (GC) based on preoperative inflammatory markers.Methods:Clinicopathological and follow-up data of 1 035 patients with stage Ⅰ-Ⅲ gastric cancer operated at He'nan Cancer Hospital between May 2015 and Oct 2016 were retrospectively collected. A nomogram was established based on prognostic factors. Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the performance of the model according to differentiation, calibration and clinical utility.Results:A total of 1 035 patients were enrolled . The median follow-up time was 41.9 months; According to the optimal cutoff value, 170 were with elevated neutrophil-to-lymphocyte ratio (NLR) and 865 with a reduced ratio; 562 in elevated platelet-to-lymphocyte ratio (PLR) vs. 473 in the reduced group; fibrinogen/albumin ratio (FAR) elevated in 108 group vs. 972 in the reduced group; 180 in the prognostic nutritional index score (PNI) elevated group and 855 in the reduced group. Two hundred and sixty-seven patients were categorized at stage Ⅰ, 334 at stage Ⅱ ,434 at stage Ⅲ. Multivariate regression analysis showed tumor location, vascular tumor thrombus, pTNM stage, FAR, PNI and NLR were independent prognostic factors (all P<0.05). The C-index of the nomogram was 0.723 (95% CI: 0.710 -0.736) and had better clinical utility than the American Joint Committee on Cancer (AJCC) 8th TNM staging system 0.693 (95% CI, 0.681 -0.705). The calibration curve of the nomogram showed that the predicted survival rate was consistent with the actual survival rate in GC patients. Compared to AJCC 8th pTNM staging system, the DCA curve indicate that the nomogram has a higher net income. Conclusion:The nomogram predicting overall survival of patients with stage Ⅰ-Ⅲ gastric cancer is established and verified , which provides better individual prediction than TNM staging system.
		                        		
		                        		
		                        		
		                        	
5.Prognostic value of combined serum fibrinogen to albumin ratio and serum CA724 after radical resection for stage Ⅱ/Ⅲ gastric cancer
Kelei HUA ; Yingkun REN ; Guangsen HAN ; Peijun WANG ; Mingke HUO ; Zhichuang DONG
Chinese Journal of General Surgery 2021;36(10):739-745
		                        		
		                        			
		                        			Objective:To explore the prognostic value of combined fibrinogen/albumin ratio (FAR) and CA724 in patients with stage Ⅱ/Ⅲ gastric cancer after radical resection.Methods:A total of 932 patients were enrolled in the study, and the best cut-off values of CEA, FAR, NLR and other variables were obtained through ROC curve analysis. According to the FAR-CA724 score, patients were divided into 3 groups: FAR-CA724=0 (CA724<3.43 ng/ml and FAR<0.083), FAR-CA724=1 (CA724≥3.43 ng/ml and FAR≥0.083) and FAR-CA724=2 (CEA≥3.43 ng/ml and FAR≥0.083).Results:After FAR-CA724 grouping, the patient's age (χ 2=12.02, P=0.002), gender (χ 2=15.91, P<0.001), tumor size (χ 2=18.22, P<0.001), hypertension (χ 2=6.35, P=0.042), tumor location (χ 2=26.09, P<0.001), degree of differentiation (χ 2=12.46, P=0.002) and pTNM staging (χ 2=6.68, P=0.035) are significantly different. Survival analysis showed that there were significant differences in OS between the three groups of patients (FAR-CA724=0, 1, and 2: 88.2%, 64.3% and 37.8%, respectively, P<0.001). By multivariate analysis FAR-CA724 is an independent risk factor affecting OS in patients with stage Ⅱ/Ⅲ gastric cancer after radical surgery. Conclusions:Preoperative FAR-CA724 may be a potential blood marker for predicting the prognosis of GC patients.
		                        		
		                        		
		                        		
		                        	
6.Identification and molecular mechanism of gastric cancer stem cells in invasion and metastasis of gastric cancer
Yongchao XU ; Tao HUANG ; Ligong TANG ; Xing LI ; Yingkun REN ; Tieqi HOU
Chinese Journal of General Surgery 2020;35(5):401-404
		                        		
		                        			
		                        			Objective:To investigate the value and molecular mechanism of gastric cancer stem cells in invasion and metastasis of gastric cancer.Methods:Gastric cancer stem cells were isolated by spheroid culture method, and the biological characteristics were identified. The role of gastric cancer stem cells in multidrug resistance, invasion and metastasis was analyzed. The important molecules involved in the biological behavior of gastric cancer stem cells were identified by gene chip. Screening of the signaling pathway revealed that anthrax toxin receptor 2 (ANTXR2)plays an important role in invasion, metastasis, glomerization and tumor formation.Results:Sox2 and Bmi1 expression in SGC7901 and MGC803 cells were significantly higher than monolayer culture cells (15.39±3.23). Oct4 express increased to (4.19±0.62). The expression levels of the dry-related genes Bmi1, Sox2 and Oct4 in SGC7901-SC cells were (3.29±0.52), (3.12±0.49), (2.58±0.35), respectively, which were higher than those of SGC7901-MN cells, Bmi1, Sox2 and Oct4, respectively. The differences were statistically significant ( t=5.392, 7.316, 6.449, all P<0.05) for (1.41±0.39), (2.04±0.33), (1.39±0.32); in primary cells XN0422-SC and in SGC7901-SC cells, miR-638 was in high expression (0.69±0.11), and miR-181b and miR-181a in low expression (0.12±0.05) and (0.15±0.07). ANTXR2 expression in SGC7901-SC cells was higher than that in SGC7901-MN cells ( t=6.216, P<0.05). The ANTXR2 positive cells in SGC7901-SC was 85.48%. The proportion of ANTXR2 positive cells in SGC7901 was 4.98%. Gastric cancer cells XN0422 and SGC7901 were affected by PLVT713, and ANTXR2 expression protein decreased. Conclusion:ANTXR effects a regulatory role by activating the Src/ERk signaling pathway, which can be used to predict the biological beharious of gastric cancer.
		                        		
		                        		
		                        		
		                        	
7.Expression of annexin A9 in gastric cancer and its effect on proliferation of gastric cancer cell line SGC-7901
Kelei HUA ; Yingkun REN ; Guangsen HAN ; Mingke HUO
Chinese Journal of General Surgery 2020;35(11):887-891
		                        		
		                        			
		                        			Objective:To investigate the expression of annexin A9(ANXA9)in gastric cancer tissues and cells and its effect on the proliferation of gastric cancer cells and the ability of subcutaneous tumorigenesis in nude mice.Methods:Immunohistochemistry and qPCR were used to detect the relationship between the expression of ANXA9 and clinicopathological parameters and prognosis in gastric cancer and paired adjacent tissues.Lentivirus transfection was used to inhibit the expression of ANXA9 in gastric cancer cell line SGC-7901. Cell counting kit-8 (CCK-8) and clone formation were used to detect the changes of proliferation of SGC7901, flow cytometry to detect the changes of SGC-7901 cell cycle, and nude mouse model bearing subcutaneous gastric cancer xenograft was established using SGC-7901 cells with stable ANXA9 knockdown to assess the effect of low expression of ANXA9 on xenograft growth.Results:Immunohistochemistry showed that the expression level of ANXA 9 was 67.1% and 30.7% in gastric cancer tissues and adjacent tissues, respectively. qPCR showed that the expression levels of ANXA 9 mRNA in gastric cancer tissues and adjacent tissues were 0.142±0.107 and 0.819±0.191, respectively. The difference was statistically significant ( P<0.05). The high expression of ANXA9 was different from the low expression group in the degree of tissue differentiation ( P<0.05), and the median survival time was 50 and 59 months, respectively. OD values of the transfected cells were 0.285±0.025, 0.386±0.031, 0.711±0.032, 1.007±0.084, 1.552±0.055 and 0.274±0.026, 0.380±0.049, 0.714±0.035, 1.106±0.081, 1.561±0.060, respectively, compared with 0.294±0.011, 0.445±0.046, 1.076±0.096, 1.588±0.095, 2.286±0.110 in NC group ( P<0.05). Cell clone formation in the transfection group was 207±12 and 225±14, lower than that in the NC group (412±14, P<0.05). After inhibiting the expression of ANXA9, the proportion of G 0/G 1 phase cells in the transfection group was 62.80% and 55.87%, respectively, significantly increased compared with 44.37% in the NC group. The proportions of S-phase cells in the transfected group were 22.74% and 21.44%, respectively, which were significantly lower than that in the NC group 29.19% ( P<0.05), after stable interference with ANXA9, the growth rate of transplanted tumors was significantly slower than that of the control group. On the 23rd day, the average volume of transplanted tumors in the two groups were (625±49) mm 3 and (303±157) mm 3, respectively, and the mass of tumor tissues in the two groups were (1.60±0.11) and (0.57±0.09) g ( P<0.05). Conclusions:Down-regulation of ANXA9 expression can inhibit the proliferation of gastric cancer cells and the ability of subcutaneous tumor formation in nude mice.
		                        		
		                        		
		                        		
		                        	
8. Transvaginal pedicled omentum pull-through combined transanal colon pull-through for the treatment of vesicorectovaginal fistula
Yong CHENG ; Gangcheng WANG ; Guangsen HAN ; Yingkun REN ; Zhimeng LI ; Jian LI ; Yanhui GU ; Shijia ZHANG ; Mingke HUO ; Zengci RUN
Chinese Journal of General Surgery 2019;34(9):791-794
		                        		
		                        			 Objective:
		                        			To evaluate surgical repair of vesicorectovaginal fistula using transvaginal pedicled omentum pull-through combined transanal colon pull-through.
		                        		
		                        			Methods:
		                        			A total of 11 patients with postoperative vesicorectovaginal fistulas complicating female reproductive system malignant tumors undergoing repairement from Aug 2013 to Aug 2018 were retrospectively analyzed. In order to isolate, protect the bladder and eliminate residual vaginal cavity using transvaginal pedicled omentum pull-through, combined transanal colon pull-through to repair vesicorectovaginal fistula.
		                        		
		                        			Results:
		                        			All the 11 patients in this group completed the operation successfully, and no air or stool passing from the vaginal after the operation. The fistula disappeared in five patients confirmed by cystography and enterograph. The average operation time was 115 min, the average blood loss was 260 ml.Incision fat liquefaction was found in two. Incision infection occurred in one. Urinary dysfunction in two. Anal stenosis was found in four patients which were healed by anal dilation.
		                        		
		                        			Conclusions
		                        			Transvaginal pedicled omentum pull-through combined transanal colon pull-through can eliminate vesicorectovaginal fistula, improve life quality and avoid colostomy. 
		                        		
		                        		
		                        		
		                        	
9.Progression-free survival related factors and the prognosis after first surgical resection for retroperitoneal liposarcoma
Mingke HUO ; Guangsen HAN ; Yingkun REN ; Yong CHENG ; Jian YANG
Chinese Journal of General Surgery 2019;34(5):389-392
		                        		
		                        			
		                        			Objective To investigate the effect of the first surgical treatment on progression-free survival (PFS)time of retroperitoneal liposarcoma and the prognosis.Methods We analyzed the clinical data of 74 cases of retroperitoneal liposarcoma from 1998 to 2016 in He'nan Cancer Hospital (Zhengzhou University Affiliated Tumor Hospital Department of General Surgery).Results The results demonstrated that progression-free survival time of the first surgical resection of retroperitoneal liposarcoma in patients related with tumor necrosis (P < 0.001),lobulated tumor (P < 0.001),symptoms (P =0.013),Ro resection (P =0.003),distant metastasis (P =0.028),postoperative chemotherapy (P =0.006) and tumor differentiation (P < 0.001).Progression-free survival time was not correlated with gender,age of first diagnosis,the invasion of adjacent organs,tumor size,operation time and combined organ resection (all P>0.05).The rate of 1-year,3-year,5-year survival time attached to PFS≤24 m and PFS >24 m were 93.7% vs.94.7,90.5% vs.80.9%,58.4% vs.74.8%(P=0.111).Conclusion The first attempt of radical resection determines progression-free survival of retroperitoneal liposarcoma,however,patients' PFS was not related with their overall survival.
		                        		
		                        		
		                        		
		                        	
10.Clinical study of pancreaticoenterostomy by separating and continuous suture in pancreatoduodenectomy
Gangcheng WANG ; Guangsen HAN ; Yingjun LIU ; Yong CHENG ; Yingkun REN ; Xianzhi LU ; Ping HUANG
Chinese Journal of Pancreatology 2016;16(1):19-22
		                        		
		                        			
		                        			Objective To investigate the effects of pancreaticoenterostomy by separating and continuous suture on pancreatoduodenectomy.Methods The clinical data of 76 patients who underwent curative pancreaticoduodenectomy from March 2002 to October 2014 in Tumor Hospital of Zhengzhou University were retrospectively analyzed.Of all the patients,43 received pancreaticoenterostomy by separating and continuous suture (study group),and the other 33 patients received BPJ anastomosis (control group).All the patients used Child reconstruction,the diagnosis of pancreatic fistula was made according to ISGPF criteria.The operation time of pancreaticoenterostomy,the incidence of hemorrhage of anastomosis and the incidence of pancreatic fistula were retrospectively analyzed.Results The age,sex,hemoglobin,albumin,total bilirubin,the incidence of co-morbidity of diabetes,extent of surgical resection between 2 groups were comparable without significant difference.In study group,the time of pancreaticoenterostomy was 11 min(8 ~ 15 min),there were 4 patients with class Ⅰ pancreatic fistula,and 1 patient with class Ⅱ pancreatic fistula.No patient developed class Ⅲ pancreatic fistula or anastomotic bleeding.In control group,the time of pancreaticoenterostomy was 16 min(12 ~25 min) which was only available for 5 patients,and no records for other patients.There were 6 patients with pancreatic fistula including 4 patients with class Ⅱ,2 patients with class Ⅲ,while no records for class Ⅰ.Four patients were found to have anastomotic bleeding.Conclusions With the pancreaticoenterostomy by separating and continuous suture method,the surgical field is fully exposed,the suture time is shortened and the incidence of anastomotic bleeding and pancreatic fistula is reduced.
		                        		
		                        		
		                        		
		                        	
            
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