1.Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection
Yihui TANG ; Zening HUANG ; Qiyue CHEN ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jianxian LIN ; Jun LU ; Longlong CAO ; Mi LIN ; Ruhong TU ; Chaohui ZHENG ; Changming HUANG
Chinese Journal of Surgery 2024;62(5):379-386
Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.
2.Clinical early warning and therapeutic interventions of hemophagocytic syndrome associated with Epstein-Barr virus infection
Jinpeng GAN ; Longlong XIE ; Xiulan LU
Chinese Pediatric Emergency Medicine 2024;31(11):818-824
Hemophagocytic syndrome,synonymous with hemophagocytic lymphohistiocytosis(HLH),represent a spectrum of hyperinflammatory response syndromes that have been the subject of intense scrutiny in terms of their etiopathogenesis and early warning strategies.Ebstein-Barr virus(EBV)-associated HLH is the most prevalent form of infection-associated secondary HLH.It is characterized by a sudden onset,rapid progression,and high mortality rate.The primary clinical features include persistent fever,often accompanied by manifestations of multi-system involvement,such as cytopenias,hepatosplenomegaly,lymphadenopathy,abnormal liver function,respiratory symptoms,neurological symptoms,and rashes.Therefore,early recognition and warning are crucial for improving the prognosis of patients with EBV-HLH.This article aimed to focus on the relationship between EBV and HLH,the diagnosis of EBV-HLH,associated warning factors,and treatment strategies.
3.Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection
Yihui TANG ; Zening HUANG ; Qiyue CHEN ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jianxian LIN ; Jun LU ; Longlong CAO ; Mi LIN ; Ruhong TU ; Chaohui ZHENG ; Changming HUANG
Chinese Journal of Surgery 2024;62(5):379-386
Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.
4.The mechanism of action and prognostic value of Dynamin 3 in gastric cancer
Ruhong TU ; Gildas Eric Sita Emmanuel ; Qing ZHONG ; Chaohui ZHENG ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jianxian LIN ; Jun LU ; Qiyue CHEN ; Longlong CAO ; Mi LIN ; Changming HUANG
Chinese Journal of Digestive Surgery 2023;22(9):1100-1112
Objective:To investigate the mechanism of action and prognostic value of Dynamin 3 (DNM3) in gastric cancer.Methods:The bioinformatic analysis, experimental study and retrospective cohort study was conducted. The clinicopathological data, fresh gastric cancer tissues, paired normal tissues and the corresponding paraffin sections of 153 gastric cancer patients who underwent radical gastrectomy in Fujian Medical University Union Hospital from January 2013 to July 2018 were collected. Tissues and the corresponding paraffin sections were subjected to quanti-tative real-time polymerase chain reaction, immunoblotting assay, flow cytometric cell cycle assay and immunohistochemical staining, respectively, and clinicopathological data were used for prognostic analysis. The stomach adenocarcinoma (STAD) dataset from the Cancer Genome Atlas (TCGA) database was collected for bioinformatic analysis. Observation indicators: (1) DNM3 gene expression in TCGA-STAD in gastric cancer; (2) mutations and copy number alterations of DNM3 in gastric cancer; (3) methylation level of promoter of DNM3 in gastric cancer; (4) relative protein expression of DNM3 and p53 in gastric cancer; (5) DNM3 correlation and enrichment analysis; (6) ratio of G0/G1 phase, S phase and G2/M phase of cell cycle progression; (7) correlation between immune cell infiltration and DNM3 in gastric cancer; (8) correlation between results of immunohistochemical (IHC) staining and clinical features; (9) analysis of independent factors influencing 5-year overall survival rate of gastric cancer patients. Measurement data with normal distribution were represented as Mean±SD, and comparison among multiple groups was conducted using the ANOVA and further comparison between two groups was conducted using the LSD. Comparison between two groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and compari-son between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the rank sum test. The Pearson correlation coefficient or Spearman correlation coefficient was used to test the correlation between groups. Univariate and multivariate analyses were conducted using the COX proportional risk regression model. The Kaplan-Meier method was used to draw survival curves and calculate survival rates, and the Log-Rank test was used for survival analysis. The Benjamini-Hochberg false discovery rate correction was used for adjusting of the P-value. Results:(1) DNM3 gene expression in TCGA-STAD. The expression levels of DNM3 gene in the 27 tumor tissues and paired normal tissues of the TCGA-STAD database were 0.775(0.605,1.161) and 1.216(0.772,1.681), showing a significant difference between them ( Z=?2.64, P<0.05). The messenger RNA (mRNA) expression levels of DNM3 gene in 48 pairs of gastric cancer tissues and paired normal tissues of the author′s center were 4.370(2.870,6.040) and 2.520(0.850,4.170), showing a significant difference between them ( Z=?4.39, P<0.05). (2) Mutations and copy number alterations of DNM3 in gastric cancer. There were 16 gastric cancer patients in the TCGA-STAD database with DNM3 mutation or somatic copy number alterations, including 6 cases with missense mutations, 1 case with truncated mutation, 8 cases with copy number gain and 1 case with copy number loss. The mRNA expression levels of DNM3 gene before and after mutation in the 370 gastric cancer patients of the TCGA-STAD database were 6.13(5.40,7.08) and 5.02(3.98,5.46), showing a significant difference between them (Log 2FC=?1.11, Z=?2.59, P<0.05). (3) Methylation level of promoter of DNM3 in gastric cancer. There were 372 gastric cancer patients in the TCGA-STAD database undergoing DNM3 methylation and mRNA examinations, and the results showed that levels of methylation and mRNA expression of DNM3 was 0.198 (-0.458, 0.301) and 6.014 (5.141, 6.628), respectively. The levels of methylation in DNM3 was negatively correlated with its mRNA expression ( r=?0.38, P<0.05). Results of follow-up in 32 patients showed that the 3-year overall survival rate of 16 cases with high levels of methylation in DNM3 and 16 cases with low levels of methylation in DNM3 was 18.8% and 41.3%, respectively, showing a significant difference between them ( hazard ratio=1.40, P<0.05). Results of immunoblot-ting assay showed that the relative expression level of DNM3 protein in the AGS cells treated with 0, 0.5, and 1.0 μmol/L of 5-azacytidin was 0.270±0.020, 0.357±0.051 and 0.599±0.039, respectively, showing a significant difference among the three groups ( F=57.84, P<0.05). The relative expression level of DNM3 protein in the HGC-27 cells treated with 0, 0.5, and 1.0 μmol/L of 5-azacytidin was 0.316±0.038, 0.770±0.031 and 0.877±0.052, respectively, showing a significant difference among the three groups ( F=156.30, P<0.05). (4) Relative protein expression of DNM3 and p53 in gastric cancer. Results of immunoblotting assay showed that the relative expression of DNM3 and p53 protein was 0.688±0.047 and 0.872±0.041 in the AGS cells transfected with pCMV-DNM3 plasmid, versus 0.249±0.029 and 0.352±0.020 in the AGS cells transfected with control plasmid, showing significant differences in the above indicators between the two types of cells ( t=13.77,19.74, P<0.05). The relative expression of DNM3 and p53 protein was 0.969±0.069 and 1.464±0.081 in the HGC-27 cells transfected with pCMV-DNM3 plasmid, versus 0.456±0.048 and 0.794±0.052 in the HGC-27 cells transfected with control plasmid, showing significant differences in the above indicators between the two types of cells ( t=10.57, 12.06, P<0.05). (5) DNM3 correlation and enrichment analysis. Results of correlation analysis showed that DNM3 was positively correlated with genes such as RBMS3, CNTN4 and PDE1A ( r=0.52, 0.52, 0.50, P<0.05) and negatively correlated with genes such as SLC25A39, PAICS and GAPDH ( r=?0.41, ?0.40, ?0.40, P<0.05) in gastric cancer. Results of gene set enrichment analysis showed that the set of genes related to ribosome and oxidative phosphorylation were upregulated in gastric cancer patients with DNM3 low expression [normalized enrichment score (NES)=?3.30, ?2.16, P<0.05], while the set of genes related to immunomodulatory interactions between lymphocytes and non-lymphoid cells were upregulated in gastric cancer patients with DNM3 high expression (NES=1.67, P<0.05). Results of gene ontology analysis showed that the low expression of DNM3 was associated with the separation of mitotic sister chromatid (No.0000070), nonsense-mediation of nuclear transcriptional mRNA catabolic process, sister chromatid separation (No.0000819), nuclear transcriptional mRNA catabolic process and regulation of oxidative phos-phorylation (NES=?2.29, ?3.10, ?2.33, ?2.56, ?2.68, P<0.05). Results of Kyoto encycl opedia of genes and genomes analysis showed that metabolic pathway related to ribosome and oxidative phosphory-lation were upregulated and crosstalked in gastric cancer with low expression of DNM3 (NES=?3.34, ?2.21, P<0.05). (6) Ratio of G0/G1 phase, S phase and G2/M phase of cell cycle progression. Results of flow cytometric cell cycle experiments showed that the proportions of G0/G1 phase, S phase and G2/M phase in the cell cycle was 65.1%±3.0%, 17.3%±3.0% and 17.6%±1.0% in the AGS cells transfected with pCMV-DNM3 plasmid, versus 53.4%±4.0%, 26.3%±2.0% and 20.3%±3.0% in the AGS cells transfected with control plasmid, showing significant differences in the proportions of G0/G1 phase and S phase in the two types of cells ( t=4.05, 4.32, P<0.05). (7) Correlation between immune cell infiltration and DNM3 in gastric cancer. Results of immune cell infiltration examination showed that the expression level of DNM3 was positively associated with mast cells, NK cells, pDCs, B cells, follicular helper T cells, effector memory T cells, T cells, central memory T cells, CD8 T cells, DC cells, macrophages, γ-δ T cells (Tgd), iDCs and eosinophils infiltration (Spearman correlation coefficients as 0.41, 0.29, 0.26, 0.20, 0.22, 0.22, 0.13, 0.16, 0.15, 0.14, 0.14, 0.17, 0.18, 0.22, P<0.05) and negatively associated with Th17 cell, Th2 cells and NK CD56 dim cells infiltration ( r=?0.18, ?0.23, ?0.10, P<0.05). (8) Correlation between results of IHC staining and clinical features. Results of IHC staining analysis showed that the IHC score of DNM3 was 3(2,4) in the 105 gastric cancer tissues, versus 6(4,9) in the 105 paired normal tissues, showing a significant difference between them ( Z=-7.35, P<0.05). There were significant differences in gender, tumor location and N stating between the 70 patients with low expression of DNM3 and the 35 patients with high expression of DNM3 ( χ2=4.29, 7.67, 6.86, P<0.05). (9) Analysis of independent factors influencing 5-year overall survival rate of gastric cancer patients. Results of multivariate analysis showed that stage pT3?4 and low IHC score of DNM3 were independent risk factors for 5-year overall survival rate of gastric cancer patients ( hazard ratio=1.91, 0.51, 95% confidence interval as 1.06?3.43, 0.26?0.98, P<0.05). The 5-year overall survival rate was 44.3% in patients with low expression of DNM3, versus 65.7% in gastric cancer patients with high expression of DNM3, showing a significant difference between them ( χ2=5.02, P<0.05). Conclusion:DNM3 is a tumor suppressor and an independent predictor of poor prognosis for gastric cancer, which may regulate gastric cancer cell cycle and immunosuppression in the tumor microenvironment through methylation.
5.Clinical value of muscle index changing value during neoadjuvant chemotherapy in predicting the prognosis of gastric cancer after radical gastrectomy
Yihui TANG ; Yubin MA ; Desiderio JACOPO ; Jianxian LIN ; Yinan LIU ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jun LU ; Qiyue CHEN ; Longlong CAO ; Chaohui ZHENG ; Amilcare PARISI ; Changming HUANG
Chinese Journal of Digestive Surgery 2021;20(9):955-966
Objective:To investigate the clinical value of muscle index changing value during neoadjuvant chemotherapy in predicting the prognosis of gastric cancer after radical gastrec-tomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 362 gastric cancer patients undergoing neoadjuvant chemotherapy combined with radical gastrectomy in 3 medical centers, including 163 cases in Fujian Medical University Union Hospital, 141 cases in the Affiliated Hospital of Qinghai University and 58 cases in St. Mary′s Hospital, from January 2010 to December 2017 were collected. There were 270 males and 92 females, aged from 26 to 79 years, with a median age of 61 years. Of 362 patients, 304 cases in Fujian Medical University Union Hospital and the Affiliated Hospital of Qinghai University were allocated into modeling group and 58 cases in St. Mary′s Hospital were allocated into validation group. Observation indicators: (1) changes of indicators including body composition parameters, tumor markers and stress status indicators in patients in modeling group during neoadjuvant chemotherapy; (2) follow-up and survival of patients; (3) analysis of risk factor affecting prognosis of patients in modeling group; (4) construc-tion and comparison of prognostic prediction models; (5) evaluation of prognostic prediction models. Follow-up was conducted using outpatient examination, telephone interview and mail communication to detect postoperative survival of patients up to April 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Univariate and multivariate analysis were performed using the COX proportional hazard model. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Results:(1) Changes of indicators including body composition parameters, tumor markers and stress status indicators in patients in modeling group during neoadjuvant chemotherapy: the subcutaneous adipose index, visceral adipose index, muscle index, carcinoem-bryonic antigen, CA19-9, body mass index, prognostic nutritional index and modified systemic inflammation score of 304 gastric cancer patients in the modeling group before neoadjuvant chemotherapy were 31.2 cm 2/m 2(range, 0.6?96.0 cm 2/m 2), 25.1 cm 2/m 2(range, 0.1?86.3 cm 2/m 2), 47.1 cm 2/m 2(range, 27.6?76.6 cm 2/m 2), 43.2 μg/L(range, 0.2?1 000.0 μg/L), 108.7(range, 0.6? 1 000.0)U/mL, 21.9 kg/m 2(range, 15.6?29.7 kg/m 2), 46.8(range, 28.6?69.0), 1.0±0.8, respectively. The above indicators of 304 gastric cancer patients in the modeling group before radical gastrec-tomy were 32.5 cm 2/m 2(range, 5.1?112.0 cm 2/m 2), 25.4 cm 2/m 2(range, 0.2?89.0 cm 2/m 2), 47.0 cm 2/m 2(range, 16.8?67.0 cm 2/m 2), 17.0 μg/L(range, 0.2?1 000.0 μg/L), 43.9 U/mL(range, 0.6?1 000.0 U/mL), 21.6 kg/m 2(range, 31.1?29.0 kg/m 2), 47.7(range, 30.0?84.0), 1.0±0.8, respectively. The changing value of above indicators of 304 gastric cancer patients in the modeling group during neoadjuvant chemotherapy were 1.4 cm 2/m 2(range, ?31.0?35.1 cm 2/m 2), 0.2 cm 2/m 2(range, ?23.5?32.6 cm 2/m 2), ?0.1 cm 2/m 2(range, ?18.2?15.9 cm 2/m 2), ?26.2 μg/L(range, ?933.5?89.9 μg/L), ?64.9 U/mL(range, ?992.1?178.6 U/mL), ?0.3 kg/m 2(range, ?9.7?7.1 kg/m 2), 0.9(range, ?27.1?38.2), 0.0±0.8, respec-tively. (2) Follow-up and survival of patients: 284 of 304 patients in the modeling group were followed up for 3 to 130 months, with a median follow-up time of 36 months. During follow-up, 130 cases died of tumor recurrence and metastasis and 9 cases died of non-tumor causes. The 5-year overall survival rate was 54.6%. Fifty-two of 58 patients in the validation group were followed up for 2 to 91 months, with a median follow-up time of 29 months. During follow-up, 21 cases died with the 5-year overall survival rate of 63.8%. (3) Analysis of risk factor affecting prognosis of patients in modeling group: results of univariate analysis showed that the postoperative pathological type and postoperative pathological staging were related factors affecting 5-year overall survival rate [ hazard ratio=1.685, 2.619, 95% confidence interval(CI): 1.139?2.493, 1.941?3.533, P<0.05] and 5-year progression free rate survival of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio=1.468, 2.577, 95% CI: 1.000?2.154, 1.919?3.461, P<0.05). Results of multivariate analysis showed that the postoperative pathological type and postoperative pathological staging were independent influencing factors for 5-year overall survival rate of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio=1.508, 2.287, 95% CI: 1.013?2.245, 1.691?3.093, P<0.05) and the postoperative patholo-gical staging was an independent influencing factor for 5-year progression free survival rate of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio= 2.317,95% CI: 1.719?3.123, P<0.05). (4) Construction and comparison of prognostic prediction models: the area under curve (AUC) of prognostic prediction model of subcutaneous adipose index changing value, visceral adipose index changing value, carcinoembryonic antigen changing value, CA19-9 changing value, body mass index changing value, prognostic nutritional index changing value, modified systemic inflammation score changing value for 304 gastric cancer patients in the modeling group were 0.549(95% CI: 0.504?0.593), 0.501(95% CI: 0.456?0.546), 0.566(95% CI: 0.521?0.610), 0.519(95% CI: 0.474?0.563), 0.588(95% CI: 0.545?0.632), 0.553(95% CI: 0.509?0.597), 0.539(95% CI: 0.495?0.584). The AUC of prognostic prediction model of muscle index changing value was 0.661(95% CI: 0.623?0.705) with significant differences to the AUC of prognostic predic-tion model of subcutaneous adipose index changing value, visceral adipose index changing value, carcinoembryonic antigen changing value, CA19-9 changing value, body mass index changing value, prognostic nutritional index changing value, modified systemic inflammation score changing value, respectively ( Z=3.960, 5.326, 3.353, 4.786, 2.455, 3.448, 3.987, P<0.05). The optimum cut-off value was 0.7 cm 2/m 2 for prognostic prediction model of muscle index changing. Kaplan-Meier survival curve showed there were significant differences of overall survival and progression free survival for gastric cancer patients with subcutaneous adipose index changing value <0.7 cm 2/m 2 and ≥0.7 cm 2/m 2 in the modeling group ( χ2 =27.510, 21.830, P<0.05). The nomogram prognostic prediction model was cons-tructed based on 3 prognostic indicators including muscle index change value combined with postoperative pathological type and postoperative pathological staging and the AUC of nomogram prognostic prediction model were 0.762(95% CI: 0.708?0.815) and 0.788(95% CI: 0.661?0.885) for the modeling group and the validation group, respectively. The AUC of postoperative pathological staging prognostic prediction model were 0.706(95% CI: 0.648?0.765) and 0.727(95% CI: 0.594?0.835)for the modeling group and the validation group, respectively. There were significant differences of the AUC between the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging and the postoperative pathological staging prognostic prediction model in the modeling group and the validation group, respectively ( Z=3.522, 1.830, P<0.05). (5) Evaluation of prognostic prediction models: the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging showed that patients with score of 0-6 were classified in the low risk group, patients with score of >6 and ≤10 were classified in the moderate-low risk group, patients with score of >10 and ≤13 were classified in the moderate-high risk group and patients with score of >13 were classified in the high risk group. Kaplan-Meier survival curve showed there were significant differences of the overall survival between the low risk group, moderate-low risk group, moderate-high risk group and high risk group patients in the modeling group and the validation group, respectively ( χ2 =75.276, 14.989, P<0.05). Results of decision making curve showed the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging had better clinical utility than the postoperative pathological staging prognostic prediction model in the modeling group and the validation group. Conclusions:The muscle index changing value of gastric cancer patient during neoadjuvant chemotherapy can be used as a prognostic indicator for gastric cancer patient prognosis after radical gastrectomy. The risk score of the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging can be used to evaluate the survival and prognosis of gastric cancer patients after radical gastrectomy.
6.Clinical effect analysis of laparoscopic radical gastrectomy for gastric cancer: a report of 4 435 cases
Jianxian LIN ; Changming HUANG ; Chaohui ZHENG ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jun LU ; Qiyue CHEN ; Longlong CAO ; Mi LIN ; Ruhong TU ; Zening HUANG ; Juli LIN
Chinese Journal of Digestive Surgery 2019;18(3):235-243
Objective To investigate the development trend,safety and clinical effects of laparoscopic radical gastrectomy (LRG) for gastric cancer.Methods The retrospective and descriptive study was conducted.The clinicopathological data of 4 435 patients with gastric cancer who underwent LRG in the Fujian Medical University Union Hospital between January 2008 and December 2017 were collected.There were 3 263 males and 1 172 females,aged (61±11)years,with a range of 12-93 years.According to the operation time,4 435 patients were divided into two periods,including 1 588 patients of the early period (2008-2012) and 2 847 patients of the later period (2013-2017).Observation indicators:(1) the clinicopathological data of patients;(2) intraoperative and postoperative situations;(3) postoperative complications;(4) follow-up and survival situations.Follow-up using outpatient examination,visit to home,mail and telephone interview was performed to detect survival of patients once every 3 months within 2 years postoperatively and once every 6 months after 2 years postoperatively up to June 2018.Survival time was from operation time to the last follow-up,death or deadline of follow-up database such as loss to follow-up or death of other diseases.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was analyzed by the t test.Measurement data with skewed distribution were represented as M (range).Count data were described as frequency or percentage,comparison between groups was analyzed using the chi-square test.Linear analysis was done using the unitary linear regression.The survival rate and survival curve were respectively calculated and drawn by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) The clinicopathological data of patients:there were 3 263 males and 1 172 females of the 4 435 patients,accounting for 73.574%(3 263/4 435) and 26.426% (1 172/4 435),respectively.TNM staging of the 4 435 patients:1 133 cases were detected early gastric cancer (T1 stage) and 3 302 cases were detected advanced gastric cancer including 518,1 431,1 353 in T2,T3 and T4a stages respectively.Linear regression analysis showed a linear correlation between the cases of LRG and operation year (R2 =0.911,P<0.05) and a gradually increasing in cases of LRG.The sex (male),cases with tumor at upper stomach,middle stomach,lower stomach,> 2 regions (tumor location),tumor diameter,cases with undifferentiated and differentiated tumor (pathological types),cases in pT1,pT2,pT3,pT4a stages (pT staging),in pN0,pN1,pN2,pN3a,pN3b stages (pN staging),in Ⅰ A,Ⅰ B,Ⅱ A,Ⅱ B,ⅢA,ⅢB,ⅢC stages (pTNM staging) were 1 204,383,302,714,189,(4.8±2.7)cm,361,1 227,382,193,418,595,588,212,255,318,215,325,137,150,172,253,267,284 in patients of the early period,and 2 059,807,530,1 128,382,(4.3±2.6) cm,976,1 871,751,325,1 013,758,1 138,444,505,486,274,616,258,378,322,528,443,302 in patients of the later period,with statistically significant differences between patients of the two periods (x2 =6.411,15.699,t =10.946,x2 =57.801,90.437,26.502,98.773,P<0.05).(2) Intraoperative and postoperative situations:the volume of intraoperative blood loss,cases with intraoperative blood transfusion,cases with Billroth Ⅰ,Billroth Ⅱ,residual stomach Roux-en-Y anastomosis,esophagogastric anastomosis,esophageal Roux-en-Y anastomosis of digestive tract reconstruction,number of lymph nodes dissected,time for initial fluid diet intake,time for initial semi-fluid diet intake,duration of postoperative hospital stay were (120±75)mL,38,599,122,0,32,835,32±13,(4.5±l.7)days,(8.6±2.5)days,(13.0± 7.3) days in patients of the early period,(104±68)mL,17,441,673,21,18,1 694,37±15,(4.1± 1.5)days,(7.9±2.8) days,(12.3±7.6) days in patients of the later period,showing statistically significant differences between patients of the two periods (t=2.169,x2 =26.843,397.185,t=-10.764,2.125,3.347,2.779,P<0.05).Further linear regression analysis showed a linear correlation between the average number of lymph nodes dissected and operation year (R2=0.826,P<0.05) and a gradually increasing in average number of lymph nodes dissected.(3) Postoperative complications:690 of 4 435 patients had postoperative complications,with an incidence rate of 15.558% (690/4 435),including 242 patients of the early period and 448 of the later period,showing no statistically significant difference (x2 =0.191,P > 0.05).Eight patients died of severe postoperative complications,with a death rate of 0.180% (8/4 435),including 5 of the early period and 3 of the later period,showing no statistically significant difference (x2 =2.485,P>0.05).Of 4 435 patients,561 had stage Ⅰ-Ⅱ complications,with an incidence rate of 12.649% (561/4 435),129 had stage Ⅲ-Ⅳ complications,with an incidence rate of 2.909%(129/4 435).There were 196 and 46 patients of the early period with stage Ⅰ-Ⅱ complications and stage Ⅲ-Ⅳ complications,365 and 83 of the later period with stage Ⅰ-Ⅱ complications and stage Ⅲ-Ⅳ complications,showing no statistically significant difference between patients of the two periods (x2 =0.211,0.001,P>0.05).(4) Follow-up and survival situations:4 250 of 4 435 patients including 1 465 of the early period and 2 785 of the later period were followed up for 1-123 months,with a median time of 37 months.The 5-year cumulative survival rate was 63.9%.The 5-year cumulative survival rate was 91.8%,80.2% and 39.5% in the stage Ⅰ,Ⅱ,Ⅲ patients,respectively,showing a statistically significant difference (x2 =810.146,P<0.05).The 5-year cumulative survival rate was 60.8% and 66.7% in patients of the early and later period,respectively with a statistically significant difference (x2 =17.887,P<0.05).Stratified analysis of TNM staging:the 5-year cumulative survival rates of stage Ⅰ A,Ⅰ B,Ⅱ A,Ⅱ B,Ⅲ A,Ⅲ B,Ⅲ C patients in the early period were 92.7%,85.6%,79.4%,74.5%,58.1%,37.6%,18.9% and 95.6%,90.4%,87.6%,79.5%,52.7%,41.2%,19.5% in patients of the later period,with no statistically significant difference (x2 =0.414,2.575,2.872,2.119,0.632,0.972,2.212,P>0.05).Conclusions Surgical volume of the LRG has shown an increasing trend year by year,and the number of lymph nodes dissected and postoperative recovery of patients are improving.LRG is a safe procedure with acceptable clinical efficacy for gastric cancer.
7.Application value of indocyanine green fluorescence imaging in lymphadenectomy of laparoscopic radical gastrectomy for gastric cancer
Ruhong TU ; Jianxian LIN ; Chaohui ZHENG ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jun LU ; Qiyue CHEN ; Longlong CAO ; Mi LIN ; Zening HUANG ; Juli LIN ; Hualong ZHENG ; Changming HUANG
Chinese Journal of Digestive Surgery 2019;18(5):466-471
Objective To investigate the application value of indocyanine green (ICG) fluorescence imaging in lymphadenectomy of laparoscopic radical gastrectomy for gastric cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 702 patients with primary gastric cancer who underwent laparoscopic radical gastrectomy and D2 lymphadenectomy in the Fujian Medical University Uuion Hospital between April and December 2017 were collected.There were 517 males and 185 females,aged from 22 to 91 years,with an average age of 61 years.Of the 702 patients,39 using ICG fluorescence imaging in the surgery and 663 not using ICG fluorescence imaging were allocated into ICG group and non-ICG group,respectively.Observation indicators:(1) surgical situations and postoperative recovery;(2) postoperative complications;(3) average number of lymph node dissected and positive lymph nodes;(4) follow-up situations.The number of lymph node dissected in the first station (No.1-7 group) and second station (No.8-12 group) were analyzed respectively.Follow-up using outpatient examination and telephone interview was performed to detect complications of patients up to June 2018.Measurement data with normal distribution were represented as Mean±SD,comparison between groups was analyzed using the t test.Measurement data with skewed distribution were described as M (range),comparison between groups was analyzed using the Mann-Whitney U test.Count data were represented as absolute number or percentage,comparison between groups was analyzed using the chi-square test.Comparisons of ordinal data were analyzed by the Mann-Whitney U test.Results (1) Surgical situations and postoperative recovery:702 patients underwent successfully laparoscopic radical gastrectomy and D2 lymphadenectomy,without injuries of important vessels and adjacent organs,without combined multiple organs resection or conversion to open surgery.Of 39 patients in the ICG group,cases undergoing total radical gastrectomy,distal subtotal gastrectomy and proximal subtotal gastrectomy,cases with Roux-en-Y esophagojejunostomy,Billroth Ⅰ anastomosis,Billroth Ⅱ anastomosis,Roux-en-Y gastrojejunostomy and esophagogastric anastomosis,operation time,volume of intraoperative blood loss,time for out-of-bed activities,time to initial anal exsufflation,time to first fluid diet intake and duration of postoperative hospital stay were 21,16,2,21,3,13,2,0,(173±28) minutes,40 mL (range,5-200 mL),(2.1±0.6)days,(3.5±1.4)days,(4.8± 1.3)days,(8.6±3.6) days.The above indexes were 363,299,1,363,27,267,1,5,(174±41)minutes,50 mL(range,0-1 750 mL),(2.2±0.8)days,(3.4± 1.1) days,(4.6± 1.5) days,(9.4± 5.0) days in the non-ICG group.There were statistically significant differences in the surgical type and digestive reconstruction method (x2 =9.550,11.388,P< 0.05) and no statistically significant difference in the operation time,volume of intraoperative blood loss,time for out-of-bed activities,time to initial anal exsufflation,time to first fluid diet intake and duration of postoperative hospital stay (t =0.221,Z =-0.651,t =0.492,-0.826,-0.842,0.995,P>0.05).(2) Postoperative complications:92 out of the 702 patients had postoperative complications,without death of complications.The incidence of complication was 15.38%(6/39) and 12.97%(86/663) in the ICG group and non-ICG group,with no statistically significant difference between the two groups (x2=0.188,P>0.05).Six patients with complications (1 of Clavien-Dindo Ⅳ,2 of Clavien-Dindo Ⅲa,3 of Clavien-Dindo Ⅰ) in the ICG group and 86 (6 of Clavien-Dindo Ⅳ,16 of Clavien-Dindo Ⅲ,61 of Clavien-Dindo Ⅱ,3 of Clavien-Dindo Ⅰ) in the non-ICG group were cured after symptomatic treatment.(3) Average number of lymph node dissected and positive lymph nodes:the average number of lymph node dissected and positive lymph nodes was 37 (range,3-112) and 1 (range,0-68) of 702 patients,38 (range,24-70) and 2 (range,0-42) in the ICG group,37 (range,3-112) and 1 (range,0-68) in the non-ICG group,with no statistically significant difference between the two groups (Z=-1.454,-0.514,P>0.05).Stratified analysis:the average number of No.1-7 group lymph nodes dissected and positive lymph nodes was 34 (range,16-67) and 2 (0-38) in the ICG group,33 (range,3-91) and 1 (range,0-56) in the non-ICG group.The average number of No.8-12 group lymph nodes dissected and positive lymph nodes was 11 (range,4-22) and 0 (range,0-13) in the ICG group,9 (range,0-31) and 0 (range,0-25) in the non-ICG group.There was a statistically significant difference in the average number of No.8-12 group lymph nodes dissected between the two groups (Z=-1.984,P<0.05).There was no statistically significant difference in the average number of No.1-7 group lymph nodes dissected,positive No.1-7 group lymph nodes and the average number of positive No.8-12 group lymph nodes between the two groups (Z =-1.302,-0.463,-0.758,P>0.05).(4) Follow-up situations:702 patients were followed up for 6-14 months,with a median time of 10 months.There was no readmission caused by postoperative complications in the two groups.Conclusion ICG fluorescence imaging in lymphadenectomy of laparoscopic radical gastrectomy for gastric cancer is beneficial to dissection of perigastric lymph nodes and increase number of lymph nodes dissected,but cannot increase operation time and incidence of postoperative complications.
8. Clinical efficacy of Da Vinci robotic total gastrectomy combined with spleen-preserving splenic hilar lymphadenectomy for gastric cancer
Longlong CAO ; Jun LU ; Jianxian LIN ; Chaohui ZHENG ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Qiyue CHEN ; Mi LIN ; Ruhong TU ; Zening HUANG ; Juli LIN ; Changming HUANG
Chinese Journal of Digestive Surgery 2019;18(9):873-878
Objective:
To investigate the clinical efficacy of Da Vinci robotic total gastrectomy combined with spleen-preserving splenic hilar lymphadenectomy for gastric cancer.
Methods:
The retrospective cross-sectional study was conducted. The clinicopathological data of 47 patients with gastric cancer who were admitted to Fujian Medical University Union Hospital from September 2016 to June 2018 were collected. There were 37 males and 10 females, aged from 23 to 75 years, with an average age of 60 years. Patients underwent Da Vinci robotic total gastrectomy combined with spleen-preserving splenic hilar lymphadenectomy. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) postoperative pathological examination; (4) follow-up. Follow-up was conducted by outpatient examination and telephone interview to detect postoperative survival of patients up to September 2018. Measurement data with normal distribution were represented as
9.Effect of unplanned reoperation on clinical efficacy and its risk factor after radical resection of gastric cancer (A report of 4 124 cases)
Ping LI ; Changming HUANG ; Chaohui ZHENG ; Jianwei XIE ; Jiabin WANG ; Jianxian LIN ; Jun LU ; Qiyue CHEN ; Longlong CAO ; Mi LIN ; Ruhong TU
Chinese Journal of Digestive Surgery 2018;17(6):564-570
Objective To explore the effect of unplanned reoperation (URO) on clinical efficacy after radical resection of gastric cancer (GC),and its causes and risk factors analysis affecting URO.Methods The retrospective case-control study was conducted.The clinicopathological data of 4 124 patients who underwent radical resection of GC in the Union Hospital of Fujian Medical University between January 2005 and December 2014 were collected.The initial operation was open or laparoscopic radical resection of GC.Observation indicators:(1) initial operation situations,results of pathologic examination and follow-up situations;(2) postoperative recovery situations;(3) causes and time interval of URO after radical resection of GC;(4) univariate analysis affecting URO after radical resection of GC;(5) multivariate analysis affecting URO after radical resection of GC.Follow-up using outpatient examination,telephone interview and Wechat was performed to detect postoperative 30-day recovery of patients.Measurement data with normal distribution were represented as (-x)±s,and comparisons between groups were done using the independent-sample t test.Count data and univariate analysis were done using the chi-square test or Fisher exact probability.Multivariate analysis was done using the logistic regression model.Results (1) Initial operation situations,results of pathologic examination and follow-up situations:① Initial operation situations of 4 124 patients,2 608 and 1 516 underwent respectively laparoscopic surgery and open surgery;2 259 and 1 865 underwent respectively total gastrectomy and distal gastrectomy.② Results of pathological examination of 4 124 patients:883,468,959 and 1 814 were respectively in T1,T2,T3 and T4a stages;1 414,571,683 and 1 456 were in N0,N1,N2 and N3 stages;1 073,825 and 2 226 were in Ⅰ,Ⅱ and Ⅲ stages.③) All the 4 124 patients were followed up within 30 days after initial operation,with a follow-up rate of 100.000%(4 124/4 124),including 52 with URO and 4 072 without URO,with a early URO rate of 1.261% (52/4 124).(2) Postoperative recovery situations:of 4 072 patients without URO,575 had postoperative complications,with an incidence of 14.121% (575/4 072);17 died after operation,with a mortality of 0.417% (17/4 072),and duration of postoperative hospital stay was (14.0±9.0) days.Of 52 patients with URO,23 had complications after reoperation,with an incidence of 44.231% (23/52);6 died after reoperation,with a mortality of 11.538% (6/52),and duration of postoperative hospital stay was (28.0± 13.0) days.There were statistically significant differences in above indicators between groups (x2=37.550,t=10.900,P<0.05).(3) Causes and time interval of URO after radical resection of GC:total time interval between initial operation and URO of 52 patients was (6.9±6.7)days.Causes of URO of 52 patients:23 (2 deaths),7,6 (2 deaths),5,5 (1 death),3,2 and 1 (death) patients were respectively due to intraperitoneal hemorrhage,anastomotic bleeding,anastomotic leakage,intra-abdominal infection,small bowel obstruction,dehiscence of abdominal incisions,enteric perforation and pancreatic fistula,and time intervals between initial operation and URO of them were respectively (3.9±3.8)days,(0.9±_0.5)days,(7.9±4.7) days,(14.9±4.6)days,(16.4±9.9) days,(10.0±6.O)days,(6.7±5.2) days and 12.0 days.(4) Univariate analysis affecting URO after radical resection of GC:results showed that age,body mass index (BMI) and volume of intraoperative blood loss were risk factors affecting URO after radical resection of GC (x2 =5.468,7.589,5.041,P<0.05).(5) Multivariate analysis affecting URO after radical resection of GC:results showed that age > 70 years old,BMI > 25 kg/m2 and volume of intraoperative blood loss > 100 mL were independent risk factors affecting occurrence of URO after radical resection of GC (odds ratio =1.950,2.288,1.867;95% confidence interval:1.074-3.538,1.230-4.257,1.067-3.267,P<0.05).Conclusions URO can increase postoperative complications and mortality,and extend duration of hospital stay after radical resection of GC.Intraabdominal bleeding,anastomotic bleeding and anastomotic leakage are the main causes affecting occurrence of URO after radical resection of GC,and age >70 years old,BMI > 25 kg/m2 and volume of intraoperative blood loss > 100 mL are independent risk factors affecting occurrence of URO after radical resection of GC.
10.Impact of preoperative comorbidities on abdominal complications after laparoscope-assisted total gastrectomy for gastric cancer
Jiabin WANG ; Chaohui ZHENG ; Ping LI ; Jianwei XIE ; Jianxian LIN ; Jun LU ; Qiyue CHEN ; Longlong CAO ; Mi LIN ; Changming HUANG
Chinese Journal of Digestive Surgery 2017;16(3):275-280
Objective To investigate the impact of preoperative comorbidities on the abdominal complications after laparoscope-assisted total gastrectomy (LATG) for gastric cancer.Methods The retrospective casecontrol study was conducted.The clinical data of 1 657 gastric cancer patients who underwent LATG at the Fujian Medical University Union Hospital between January 2008 and December 2015 were collected.There were 175 patients with postoperative abdominal complications,including 78 without preoperative comorbidities and 97 with preoperative comorbidities (52 with 1 comorbidity,30 with 2 comorbidities and 15 with more than 3 comorbidities).Analysis method and observation indicators:(1) risk factors analysis of abdominal complications after LATG;(2) risk assessment of abdominal complications after LATG:independent influencing factors of risk factors analysis were expressed as dependent variables,alignment diagram was built and then consistency index was calculated;(3) comparisons of abdominal complications among the patients with different kinds of comorbidities after LATG;(4) multivariate analysis of abdominal complications in patients with comorbidities after LATG;(5)follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival of patients up to May 2016.The univariate analysis and multivariate analysis were respectively done using the chi-square test and Logistic regression model.The survival rate was calculated by the Kaplan-Meier method.Results (1) Risk factors analysis of abdominal complications after LATG:results of univariate analysis showed that age,body mass index (BMI),number of preoperative comorbidities,operation time and estimated volume of intraoperative blood loss were related factors affecting abdominal complications of patients after LATG (X2 =4.487,16.602,10.361,4.567,7.482,P<0.05).Results of multivariate analysis showed that BMI,number of preoperative comorbidities and estimated volume of intraoperative blood loss were independent factors affecting abdominal complications of patients after LATG [OR =1.966,1.204,1.423,95%confidence interval (CI):1.355-2.851,1.014-1.431,1.013-1.999,P<0.05].(2) Risk assessment of abdominal complications after LATG:BMI,number of preoperative comorbidities and estimated volume of intraoperative blood loss were expressed as dependent variables,and the alignment diagram on risk prediction of abdominal complications after LATG was built,with a consistency index of 0.703.(3) Comparisons of abdominal complications among the patients with different kinds of comorbidities after LATG:numbers of patients without comorbidity,with 1 comorbidity,2 comorbidities and ≥3 comorbidities were detected in 21,8,13,3 patients with intra-abdominal infection and 13,10,9,5 patients with anastomotic leakage and 6,3,6,2 patients with intra-abdominal bleeding,respectively,with statistically significant differences (X2 =10.677,10.436,9.245,P<0.05).(4) Multivariate analysis of abdominal complications in patients with comorbidities after LATG:BMI ≥25 kg/m2 and estimated volume of intraoperative blood loss > 82 mL were independent risk factors affecting abdominal complications of patients with preoperative comorbidities after LATG (OR =2.104,1.771,95% CI:1.307-3.387,1.146-2.738,P<0.05).(5) Follow-up situations:of 1 657 patients,1 568 were followed up for 4-99 months,with a median time of 47 months.Ninety-seven patients with preoperative comorbidities undergoing LATG had postoperative abdominal complications and were followed up.During follow-up,5-year survival rate of patients was 58.1%,and 5-year survival rate of 97 patients with preoperative comorbidities undergoing LATG and with postoperative abdominal complications was 57.4%.Conclusion Preoperative comorbidities are independent factors affecting abdominal complications of patients after LATG.

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