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.Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study
Shuqin ZHANG ; Zhouqiao WU ; Bowen HUO ; Huining XU ; Kang ZHAO ; Changqing JING ; Fenglin LIU ; Jiang YU ; Zhengrong LI ; Jian ZHANG ; Lu ZANG ; Hankun HAO ; Chaohui ZHENG ; Yong LI ; Lin FAN ; Hua HUANG ; Pin LIANG ; Bin WU ; Jiaming ZHU ; Zhaojian NIU ; Linghua ZHU ; Wu SONG ; Jun YOU ; Su YAN ; Ziyu LI
Chinese Journal of Gastrointestinal Surgery 2024;27(3):247-260
Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.
3.Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study
Shuqin ZHANG ; Zhouqiao WU ; Bowen HUO ; Huining XU ; Kang ZHAO ; Changqing JING ; Fenglin LIU ; Jiang YU ; Zhengrong LI ; Jian ZHANG ; Lu ZANG ; Hankun HAO ; Chaohui ZHENG ; Yong LI ; Lin FAN ; Hua HUANG ; Pin LIANG ; Bin WU ; Jiaming ZHU ; Zhaojian NIU ; Linghua ZHU ; Wu SONG ; Jun YOU ; Su YAN ; Ziyu LI
Chinese Journal of Gastrointestinal Surgery 2024;27(3):247-260
Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.
4.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.
5.Expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances
Jinfeng WANG ; Shuai CHEN ; Zhuo HE ; Jinhai ZHENG ; Mingjing PENG ; Jinguan LIN ; Junjun LI ; Man XIA ; Hongyu DENG ; Shun DENG ; Rilin DENG ; Haizhen ZHU ; Chaohui ZUO
Cancer Research and Clinic 2023;35(6):451-456
Objective:To explore the expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances.Methods:The clinical data of 57 patients diagnosed as pancreatic ductal carcinoma (PDAC) at the Affiliated Cancer Hospital of Xiangya Medical College of Central South University from January 2014 to December 2018 were retrospectively analyzed. The relative expressions of LINC00673 in pancreatic cancer tissues and paracancerous normal tissues (within 3 cm from the edge of cancer tissues) were examined by using quantificational reverse transcription-polymerase chain reaction (qRT-PCR). The ISG15 protein expressions in pancreatic cancer tissues and paracancerous normal tissues were examined by using immunohistochemistry. The difference in LINC00673 expression between ISG15 protein positive and negative patients was compared. The correlation between LINC00673 and ISG15 protein expressions in pancreatic cancer was analyzed by Spearman rank correlation analysis. Moreover, the correlations of LINC00673 and ISG15 protein expressions with clinical stage and pathological classification of pancreatic cancer patients were analyzed.Results:The positive expression of ISG15 protein in pancreatic cancer tissues was 40.4% (23/57), which was higher than that in paracancerous normal tissues [15.8% (9/57)] ( χ2 = 7.90, P = 0.004), and the relative expression of LINC00673 in pancreatic cancer tissues was 0.99±0.36, which was lower than that in paracancerous normal tissues (1.26±0.41) ( t = 4.80, P < 0.001). For 23 (40.4%) ISG15-positive patients and 34 (59.7%) ISG15-negative patients, the relative expression of LINC00673 was 0.77±0.46 and 0.45±0.27 ( P < 0.001). Spearman analysis showed that there was a correlation between LINC00673 and ISG15 protein expressions ( ρ = -0.429, P = 0.001). The relative expression of LINC00673 decreased in patients with low differentiated or undifferentiated tumor, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between LINC00673 expression and patients' age, tumor site, preoperative CA199 level, and TNM stage (all P > 0.05); ISG15 protein expression increased in patients with low differentiated or undifferentiated tumor, TNM stage Ⅲ-Ⅳ, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between ISG15 protein expression and patients' gender, age, tumor site, and preoperative CA199 level (all P > 0.05). Conclusions:The expression of LINC00673 in pancreatic cancer is related to vascular invasion, tumor differentiation degree and lymph node metastasis, and the expression of ISG15 in pancreatic cancer is related to vascular invasion, tumor differentiation degree, lymph node metastasis and TNM stage. The combined detection of LINC00673 and ISG15 protein could be a valuable prognostic indicator for pancreatic cancer. The therapies targeting LINC00673 and ISG15 protein signaling pathways are expected to be a potential option for immunotherapy of pancreatic cancer.
6.Learning curve analysis and influencing factors of operation time of laparoscopic sleeve gastrectomy
Zhixin SHANGGUAN ; Qing ZHONG ; Yiming JIANG ; Chaohui ZHENG ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jun LU ; Jianxian LIN ; Changming HUANG
Chinese Journal of Digestive Surgery 2023;22(8):996-1002
Objective:To investigate the influencing factors of operation time for laparos-copic sleeve gastrectomy (LSG) and analyze the learning curve of LSG in sarcopenic obesity (SO) and non-sarcopenic obesity (NSO).Methods:The retrospective cohort study was conducted. The clinical data of 240 obesity patients who underwent LSG in the Fujian Medical University Union Hospital from January 2018 to June 2022 were collected. There were 52 males and 188 females, aged (30±8)years. Patients underwent L3 vertebral body horizontal axial computer tomography (CT) scanning before and after receiving LSG to accurately segment muscles and fats. Observation indicators: (1) treatment and follow-up; (2) influencing factors of operation time for LSG; (3) cumulative sum (CUSUM) of learning curve; (4) comparison of clinical data between patients in the initial and profi-cient stages. Measurement data with normal distribution were represent as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(IQR), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Univariate and multivariate analyses were conducted using the Logistic regression model. The CUSUM of learning curve was calculated and the fitting process was conducted on scatter plot of learning curves. Results:(1) Treatment and follow-up. Of the 240 patients, there were 97 cases of SO and 143 cases of NSO. All 240 patients underwent LSG successfully, without conversion to open surgery. The operation time of 240 patients was (108±23)minutes. None of patient died during the perioperative period and all patients underwent follow-up during the postoperative 6 months. (2) Influencing factors of operation time for LSG. Results of multivariate analysis showed that SO was an independent factor influencing operation time for LSG ( odds ratio=2.207, 95% confidence interval as 1.207-4.038, P<0.05). (3) CUSUM of learning curve. Results of CUSUM of operation time in patients of SO and NSO showed that the best fit equation of patients of SO was y=-4E-08x 6+1E-05x 5-0.001 1x 4+0.063 1x 3-1.89x 2+28.126x-48.671 (x means the number of surgical cases), with goodness-of-fit R 2 as 0.833, and the best fit equation of patients of NSO was y=3E-09x 6-1E-06x 5+0.000 2x 4-0.010 9x 3+0.063 8x 2+12.053x-65.025 (x means the number of surgical cases), with goodness-of-fit R 2 as 0.716. Based on the trend of CUSUM of learning curve of operation time, the peak value of number of surgical cases in patients of SO and NSO was 81 and 36, respec-tively, which was used to divide the learning curve as two stages of the initial stage and the proficient stage. (4) Comparison of clinical data between patients in the initial and proficient stages. ① Of the 97 patients of SO, there were 81 cases and 16 cases in the initial stage and the proficient stage of LSG, with the operation time, postoperative duration of hospital stay as (119±23)minutes, (5.9±2.3)days and (106±21)minutes, (4.7±0.5)days, showing significant differences between them ( t=2.074, 2.147, P<0.05). ②Of the 143 patients of NSO, there were 36 cases and 107 cases in the initial stage and the proficient stage of LSG, with gender (female), height, preoperative body mass, defatted body mass, operation time, postoperative duration of hospital stay, body mass at postoperative 6 month, body mass index (BMI) at postoperative 6 month, percentage of excess weight loss (EWL%) at postoperative 6 month, cases with EWL% >100% at postoperative 6 month, excess BMI at post-operative 6 month as 20, (170±10)cm, (110±25)kg, (57±12)kg, (108±22)minutes, (6.1±1.6)days, (80±16)kg, (27.63±4.22)kg/m2, 83%±35%, 9, 1.99(6.03)kg/m2 and 87, (164±8)cm, (99±20)kg, (52±12)kg, (100±19)minutes, (4.7±1.1)days, (71±16)kg, (25.89±4.48)kg/m2, 103%±42%, 48, 0.31(5.82)kg/m2, showing significant differences between them ( χ2=9.484, t=3.266, 2.424, 2.141, 2.137, 5.821, 2.740, 1.993, -2.524, χ2=4.432, Z=-2.300, P<0.05). Conclusions:SO is an independent factor influencing operation time for LSG. It is suggested that the surgeons need to finish 81 cases and 36 cases master LSG in patients of SO and NSO.
7.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.
8.Construction and application value of a predictive model for prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer
Zhen XUE ; Hualong ZHENG ; Jia LIN ; Jun LU ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jianxian LIN ; Qiyue CHEN ; Chaohui ZHENG ; Changming HUANG
Chinese Journal of Digestive Surgery 2023;22(12):1456-1466
Objective:To investigate the construction and application value of a predictive model for prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 534 patients who underwent Da Vinci robotic radical gastrectomy for gastric cancer in the Fujian Medical University Union Hospital from August 2016 to August 2021 were collected. There were 389 males and 145 females, aged (60±11)years. All 534 patients were randomly divided into the training dataset of 374 cases and the validation dataset of 160 cases with a ratio of 7∶3 based on random number method in the SPSS 25.0 software. Observation indicators: (1) incidence of prolonged surgical duration; (2) intraoperative and postoperative conditions in patients with prolonged surgical duration and without prolonged surgical duration; (3) complications in patients with prolonged surgical duration and without prolonged surgical duration; (4) analysis of risk factors influencing prolonged surgical duration; (5) construction and evaluation of an artificial neural network predictive model for pro-longed surgical duration. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample 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 per-centages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparametric test. Univariate and multivariate analyses were conducted using the Logistic regression model. Based on the results of univariate analysis, a multilayer perceptron was employed to train an artificial neural network pre-dictive model for prolonged surgical duration. The receiver operating characteristic (ROC) curve was drawn, and the area under curve (AUC), the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were used to assess the model′s performance. Results:(1) Incidence of prolonged surgical duration. Of 534 patients, 284 cases underwent total gastrectomy, and 250 cases underwent distal gastrectomy, with operation time of (206±42)minutes and (187±36)minutes, res-pectively. Cases with prolonged surgical duration and without prolonged surgical duration who under-went total gastrectomy were 41 and 243, and cases with prolonged surgical duration and without prolonged surgical duration who underwent distal gastrectomy were 40 and 210. The gender (male, female), age, body mass index (BMI), tumor diameter, tumor location (upper stomach, middle stomach, lower stomach, mixed type), cases with neoadjuvant therapy, cases with preoperative American Society of Anesthesiologists (ASA) score as 1, 2, 3, cases with clinical T staging as stage T1, stage T2, stage T3, stage T4a, cases with clinical N staging as stage N0, stage N1, stage N2, stage N3, cases with clinical TNM staging as stage Ⅰ, stage Ⅱ, stage Ⅲ, cases with surgical resection scope as total gastrec-tomy or distal gastrectomy, cases with digestive tract reconstruction method as Billroth-Ⅰ anasto-mosis, Billroth-Ⅱ anastomosis, Roux-en-Y anastomosis, cases with surgeon experiences as ≤20 cases or >20 cases were 61,20, (61±9)years, (24±3)kg/m2, 4.0(2.5, 5.0)cm, 34, 10, 33, 4, 1, 3, 73, 5, 3, 6, 26, 46, 14, 41, 19, 7, 5, 13, 63, 41, 40, 1, 33, 47, 5, 76 in the 81 patients with prolonged surgical duration, versus 328, 125, (60±11)years, (23±3)kg/m2, 3.5(2.0, 5.0)cm, 129, 71, 227, 26, 6, 45, 382, 26, 73, 100, 118, 162, 211, 180, 52, 10, 138, 108,207, 243, 210, 13,200, 240, 15, 438 in the 453 patients without prolonged surgical duration, showing significant differences in the BMI, clinical T staging, clinical N staging, clinical TNM staging ( t=-3.68, Z=-4.63, -5.53, -5.56, P<0.05), and no significant difference in the gender, age, tumor diameter, tumor location, preoperative ASA score, surgical resec-tion scope, digestive tract reconstruction method, and surgeon experiences ( χ2=0.29, t=-0.95, Z=-1.27, χ2=5.92, Z=-1.46, χ2=0.25, 1.35, 0.87, P>0.05). There was no significant difference in cases with neoadjuvant therapy between them ( P>0.05). (2) Intraoperative and postoperative conditions in patients with prolonged surgical duration and without prolonged surgical duration. The operation time, volume of intraoperative blood loss, the number of lymph nodes dissected, time to postopera-tive first ambulation, time to postoperative anal exhaust, time to postoperative first intake of liquid diet, time to postoperative first intake of semi-liquid diet, duration of postoperative hospital stay were (261±34)minutes, 50(30, 50)mL, 39±15, (2.3±0.6)days, (3.4±0.9)days, (4.1±1.2)days, (5.7±1.2)days, 8.0(7.0, 9.0)days in the 81 patients with prolonged surgical duration, versus (186±29)minutes, 30(20,50)mL, 42±14, (2.2±0.6)days, (3.4±0.8)days, (4.1±1.1)days, (5.7±1.4)days, 8.0(7.0, 9.0)days in the 453 patients without prolonged surgical duration, showing significant differences in operation time, volume of intraoperative blood loss ( t=-20.46, Z=-3.32, P<0.05), and no significant difference in the number of lymph nodes dissected, time to postoperative first ambulation, time to postopera-tive anal exhaust, time to postoperative first intake of liquid diet, time to first intake of semi-liquid diet, duration of postoperative hospital stay ( t=1.87, -0.87, -0.16, 0.28, 0.03, Z=-1.45, P>0.05). (3) Complications in patients with prolonged surgical duration and without prolonged surgical duration. The overall incidence of complications, incidence of surgical complications (abdominal infection, anastomotic fistula, abdominal bleeding, incision-related complications, intestinal obstruction, lymphatic fistula), incidence of medical complications (pulmonary infection, liver-related complications) were 22.22%(18/81), 0, 0, 2.47%(2/81), 0, 8.64%(7/81), 1.23%(1/81), 12.35%(10/81), 1.23%(1/81) in the 81 patients with prolonged surgical duration, versus 13.47%(61/453), 2.65%(12/453), 0.44%(2/453), 1.77%(8/453), 0.44%(2/453), 3.31%(15/453), 0, 7.28%(33/453), 1.55%(7/453) in the 453 patients without prolonged surgical duration, showing a significant difference in the overall incidence of complications ( χ2=4.18, P<0.05), and no significant difference in the incidence of abdo-minal infection, anastomotic fistula, abdominal bleeding, incision-related complications, intestinal obstruction, lymphatic fistula, liver-related complications ( P>0.05). There was no significant difference in the incidence of pulmonary infection between them ( χ2=2.38, P>0.05). (4) Analysis of risk factors influencing prolonged surgical duration. Results of univariate analysis showed that BMI ≥25 kg/m2, tumor located in the lower stomach, clinical T3-T4a stage, clinical N1-N3 stage were correlated factors influencing prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer ( odds ratio=1.88, 0.40, 6.24, 6.51, 3.08, 3.39, 17.15, 95% confidence interval as 1.03-3.42, 0.21-0.76, 1.40-27.76, 1.50-28.30, 1.43-6.60, 1.29-8.92, 4.84-60.74, P<0.05). Results of multivariate analysis showed that BMI ≥25 kg/m2, clinical T3 stage, clinical N3 stage were independent risk factors influencing prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer ( odds ratio=2.31, 4.97, 11.08, 95% confidence interval as 1.19-4.46, 1.05-23.55, 2.72-45.13, P<0.05). (5) Construction and evaluation of an artificial neural network predictive model for pro-longed surgical duration. The BMI, tumor location, clinical T staging, and clinical N staging were incorporated into a multilayer perceptron to construct an artificial neural network predictive model for prolonged surgical duration. Results of ROC curve showed that the AUC, accuracy, sensitivity, specificity, positive predictive value, negative predictive value of the predictive model in the training dataset were 0.73 (95% confidence interval as 0.68-0.78), 91.4%, 68.1%, 94.8%, 65.3%, 95.4%. The above indicators of the predictive model in the validation dataset 0.72 (95% confidence interval as 0.65-0.79), 88.1%, 67.6%, 93.7%, 74.2%, 91.5%. Conclusions:BMI ≥25 kg/m2, clinical T3 stage, clinical N3 stage are independent risk factors influencing prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer. The artificial neural network predictive model con-structed based on BMI, tumor location, clinical T staging, and clinical N staging can effectively predict patients at high risk of prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer.
9.Femoral neck system and cannulated compression screw fixation in the treatment of femoral neck fracture in the young and middle-aged patients: efficacy comparison
Jiajie LIU ; Dongze LIN ; Peisheng CHEN ; Chaohui LIN ; Bin CHEN ; Ke ZHENG ; Shunze ZHENG ; Susu TANG ; Fengfei LIN
Chinese Journal of Trauma 2023;39(8):721-729
Objective:To compare the efficacy of femoral neck system (FNS) and cannulated compression screw (CCS) in the treatment of femoral neck fracture in the young and middle-aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 91 patients with femoral neck fracture admitted to Fuzhou Second Hospital from July 2020 to December 2021, including 52 males and 39 females; aged 23-65 years [(48.9±10.3)years]. Garden classification of the fracture found that 31 patients were with type I, 9 with type II, 12 with type III and 39 with type IV. Pauwels classification of the fracture found that 7 patients were with type I, 33 with type II and 51 with type III. A total of 53 patients were treated with FNS fixation (FNS group) and 38 patients with CCS fixation (CCS group). The operation time, intraoperative blood loss, Haidukewych fracture reduction quality, hospitalization time, Barthel index, fracture healing time, and weight-bearing time were compared between the two groups. The hip function was assessed by Harris hip score in both groups at postoperative 3 months, 6 months and 1 year and at the final follow-up. The incidences of postoperative complication and secondary surgery were also compared between the two groups.Results:All the patients were followed up for 15-31 months [(22.2±5.5)months]. There were no significant differences in the operation time, Haidukewych fracture reduction quality, hospitalization time, or Barthel index (all P>0.05). The intraoperative blood loss in the FNS group was 50.0(20.0,85.0)ml, which was more than that in the CCS group [20.0(10.0,50.0)ml] ( P<0.01). The fracture healing time, partial weight-bearing time, and full weight-bearing time in the FNS group [4.0(3.0,5.0)months, 3.0(2.0,3.0)months, 5.0(4.5,6.0)months] were shorter than those in the CCS group [6.0(5.0,7.0)months, 3.0(2.8,4.0)months, 6.0(6.0,7.0)months] (all P<0.01). The Harris hip score at postoperative 3 months, 6 months and 1 year and at the final follow-up were 74.0(71.0,77.0)points, 87.0(84.0,88.5)points, 91.0(88.0,95.0)points, and 94.0(91.0,96.0)points in the FNS group, significantly higher than those in the CCS group [73.0(70.0,74.0)points, 82.5(79.8,87.0)points, 88.0(83.5,91.0)points, 89.0(84.0,93.0)points] (all P<0.05 or 0.01). There were no statistically significant differences in the incidences of postoperative complication or secondary surgery between the two groups (all P>0.05). Conclusion:Compared with CCS, FNS can shorten fracture healing time, allow patients to carry full weight as soon as possible, and significantly improve hip function in the treatment of middle-aged and young adults with femoral neck fracture, although there is more intraoperative blood loss.
10.Reduction of valgus-impacted femoral neck fractures by Schanz screw combined with rod stick technique
Dongze LIN ; Peisheng CHEN ; Chaohui LIN ; Bin CHEN ; Ke ZHENG ; Fengfei LIN
Chinese Journal of Orthopaedics 2023;43(14):941-950
Objective:To investigate the clinical efficacy of the femoral neck system (FNS) after the reduction of the Schanz screw combined with the rod stick technique in the treatment of valgus-impacted femoral neck fracture.Methods:A retrospective analysis of clinical data from 66 patients with valgus-impacted femoral neck fractures from December 2019 to November 2021 has been performed. All patients were treated with the Femoral Neck System. Auxiliary reduction group (using the Schanz screw and rod stick technique), including 32 cases, 9 males and 23 females with an average age of 52.7±12.0 years (range, 28-77 years); 14 patients on the left side and 18 patients on the right side; body mass index 23.1±2.6 kg/m 2. Manual reduction group (using the traditional Flynn closed reduction technique), including 34 cases, 18 males and 16 females with an average age of 52.1±12.7 years (range, 26-75 years); 18 patients on the left side and 16 patients on the right side; body mass index 23.4±2.3 kg/m 2. The surgery time, intraoperative blood loss, complications, and Harris hip score at the last follow-up were collected and compared between the two groups. Preoperative and postoperative abduction angle and posterior tilt angle were measured in the anterior-posterior and lateral positions of the hip, as well as the length of the femoral neck shortening at the last follow-up. Pearson analysis was used to evaluate the correlation between preoperative and postoperative abduction angle and posterior tilt angle, the length of femoral neck shortening, and Harris hip score. Results:There were no significant differences in baseline data such as gender, age, side of injury, height, weight, and body mass index, and the surgery time and intraoperative blood loss between auxiliary reduction group and manual reduction group ( P>0.05). All 66 cases with a mean follow-up of 20.4 months (ranges 12-29 mouths). The fracture healing time was 5.0±0.9 weeks in the auxiliary reduction group and 4.9±0.8 weeks in the manual reduction group ( t=-0.41, P>0.05). There were no significant statistical difference in the preoperative abduction angle and preoperative posterior tilt angle between the auxiliary reduction group and the manual reduction group ( P>0.05). The postoperative abduction angle and posterior tilt angle of the auxiliary reduction group (1.8°±3.1°, 1.2°±3.0°) were significantly lower than those of the manual reduction group (13.7°±6.5°, 6.8°±4.1°, t=-9.55, P<0.001; t=-7.42, P<0.001). Preoperatively, 61 cases (92%) were associated with a posterior tilt of the femoral head, and 30 (46%) of them had a posterior tilt angle of more than 10°. The length of femoral neck shortening at the last follow-up and the moderate and severe femoral neck shortening rate postoperatively in the auxiliary reduction group (1.4±2.1 mm, 0, and 3%) were significantly lower than those in the manual reduction group (8.1±4.8 mm, 38%, and 32%, P<0.05). Harris hip score at the last follow-up in the auxiliary reduction group 91.1±4.5 was significantly higher than those in the manual reduction group 85.5±5.4 ( t=4.54, P<0.001). The postoperative abduction angle and length of femoral neck shortening showed correlations with the Harris hip score respectively ( r=-0.551, -0.743; P<0.001). In the auxiliary reduction group, 1 case of broken temporary fixed Kirschner wire was removed by nucleus pulposus forceps, and the fracture site healed after surgery. In 2 cases, the Schanz screw loosened and pulled out during the reduction process, and the successful reduction was achieved after increasing the depth of the Schanz screw insertion, and no peri-Schanz screw fracture occurred. After surgery, 3 cases (1 case in the auxiliary reduction group and 2 cases in the manual reduction group) developed avascular necrosis of the femoral head (18 months, 18 months, and 2 years after surgery, respectively), femoral head collapse and severe shortening of the femoral neck, all of which underwent total hip arthroplasty. Conclusion:FNS after the reduction of the Schanz screw combined with the rod stick technique in the treatment of valgus-impacted femoral neck fracture has the advantages of effectively correcting preoperative abduction angle and posterior tilt angle and reducing the length of femoral neck shortening, and it can obtain satisfactory short and medium-term clinical efficacy.

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