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Objective:To investigate the short-term outcomes of totally robotic surgical system and robotic surgical system assisted radical gastrectomy for gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 290 patients who under-went robotic surgical system radical gastrectomy for gastric cancer in the First Affiliated Hospital of Army Medical University from January 2018 to November 2021 were collected. There were 208 males and 82 females, aged 58 (range, 24?84)years. Of the 290 patients, 125 patients undergoing totally robotic surgical system radical gastrectomy combined with reconstruction of digestive tract were divided into the totally robot group, and 165 patients undergoing robotic surgical system radical gastrectomy combined with a small midline incision-assisted reconstruction of digestive tract were divided into the robotic-assisted group. Observation indicators: (1) surgical and postoperative situations; (2) postoperative complications. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the non-parameter rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Surgical and postoperative situations. The operation time, volume of intraoperative blood loss, length of incision, duration of postoperative analgesic using, time to postoperative gastric tube removal, time to postoperative initial water intake, time to postoperative first anal flatus, duration of post-operative hospital stay were (246±43)minutes, (104±51)mL, 4(range, 3?6)cm, (2.2±0.5)days, 36(range, 10?112)hours, 62(range, 32?205)hours, 63(range, 18?138)hours, 8(range, 6?50)days in patients of the totally robot group, versus (296±59)minutes, (143±87)mL, 6(range, 3?13)cm, (3.6±0.7)days, 42(range, 12?262)hours, 90(range, 18?262)hours, 80(range, 16?295)hours, 9(range, 6?63)days in patients of the robotic-assisted group, showing significant differences in the above indicators between the two groups ( t=8.04, 4.42, Z=?13.98, t=18.46, Z=?5.47, ?5.87, ?6.14, ?4.04, P<0.05). (2) Post-operative complications. Cases with systemic related complications and cases with pulmonary infection were 7 and 4 in patients of the totally robot group, versus 31 and 16 in patients of the robotic-assisted group, showing significant differences in the above indicators between the two groups ( χ2=10.86, 4.68, P<0.05). Further analysis showed that there were significant differences in age ≥60 years, body mass index ≥25 kg/m 2, tumor diameter ≥3 cm, TNM staging as stage Ⅲ of cases with postoperative complications between the totally robot group and the robotic-assisted group ( odds ratio=0.44, 0.17, 0.40, 0.31, 95 confidence interval as 0.20?1.00, 0.03?0.88, 0.18?0.89, 0.11?0.84, P<0.05). Conclusion:Totally robotic surgical system radical gastrectomy for gastric cancer is safe and feasible with advantages of minimal trauma and quick recovery, especially for patients as age ≥60 years, body mass index ≥25 kg/cm 2, tumor diameter ≥3 cm and TNM stage Ⅲ in complication controlling.
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Objective:To investigate the safety and short-term efficacy of laparoscopic pro-ximal gastrectomy (LPG) for proximal gastric cancer and adenocarcinoma of esophagogastric junction.Methods:The retrospective cohort study was conducted. The clinicopathological data of 385 patients with proximal gastric cancer and adenocarcinoma of esophagogastric junction who underwent LPG in the 15 medical centers, including the First Affiliated Hospital of Xiamen University et al, from January 2014 to March 2022 were collected. There were 304 males and 81 females, aged (63±9)years. Of the 385 patients, 335 cases undergoing LPG were divided into the laparoscopic group and 50 cases undergoing open proximal gastrectomy were divided into the open group. Observation indicators: (1) intraoperative and postoperative situations; (2) follow-up; (3) stratified analysis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Intraoperative and postoperative situations. The operation time, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, cases with postoperative pathological staging as stage 0?Ⅰ and stage Ⅱ?Ⅲ, duration of postoperative hospital stay, cases with postoperative early complications were (212±96)minutes, 270, 65, 177, 107, 10(range, 8?14)days, 40 in patients of the laparoscopic group, with 51 cases missing the data of postoperative pathological staging. The above indicators were (174±90)minutes, 39, 11, 22, 28, 10(range, 8?18)days, 10 in patients of the open group. There were significant differences in the opera-tion time and postoperative pathological staging between the two groups ( t=2.62, χ2=5.93, P<0.05), and there was no significant difference in the reconstruction of digestive tract, duration of post-operative hospital stay, postoperative early complications between the two groups ( χ2=0.19, Z=0.40, χ2=2.50, P>0.05). (2) Follow-up. Of the 385 patients,202 cases were followed up during the post-operative 12 months, including 187 cases in the laparoscopic group and 15 cases in the open group. Cases with reflux esophagitis, cases with esophageal anastomotic stenosis were 48, 11 in patients of the laparoscopic group, versus 5, 2 in patients of the open group, showing no significant difference in the above indicators between the two groups ( P>0.05). The body mass index (BMI), hemoglobin (Hb), albumin (Alb) at postoperative 6 months and 12 months were (21±3)kg/m 2, (130±15)g/L, (40±4)g/L and (21±3)kg/m 2, (132±14)g/L, (41±4)g/L in patients of the laparoscopic group, versus (21±3)kg/m 2, (121±19)g/L, (37±5)g/L and (21±3)kg/m 2, (125±21)g/L, (43±6)g/L in patients of the open group. There were significant differences in postoperative Hb between the two groups ( Fgroup=5.88, Ftime=5.49, Finteraction=19.95, P<0.05) and there were significant differences in time effect of postopera-tive BMI and Alb between the two groups ( Ftime=9.53, 49.88, P<0.05). (3) Stratified analysis. ① Incidence of postoperative of reflux esophagitis and esophageal anastomotic stenosis in patients with different reconstruction of digestive tract. Of the 202 patients, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis were 168 and 34, respectively. The incidence rates of postoperative of reflux esophagitis were 26.79%(45/168)and 23.53%(8/34)in cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, showing no significant difference between them ( χ2=0.16, P>0.05). Cases undergoing esophageal anastomotic stenosis were 13 in patients with reconstruction of diges-tive tract as esophagogastric anastomosis. ② The BMI, Hb, Alb in patients with different reconstruc-tion of digestive tract. The BMI, Hb, Alb were (24±3)kg/m 2, (135±20)g/L, (41±5)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis before the operation, versus (23±3)kg/m 2, (130±19)g/L, (40±4)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis before the operation, showing no significant difference between them ( t=1.44, 1.77, 1.33, P>0.05). The BMI, Hb, Alb at postoperative 6 months and 12 months were (21±3)kg/m 2, (128±16)g/L, (39±4)g/L and (21±3)kg/m 2, (131±16)g/L, (41±4)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis, versus (20±4)kg/m 2, (133±13)g/L, (43±3)g/L and (21±3)kg/m 2, (135±12)g/L, (44±3)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis. There were significant differences in the group effect and time effect of postoperative Alb between patients with different reconstruction of diges-tive tract ( Fgroup=15.82, Ftime=5.43, P<0.05), and there was also a significant difference in the time effect of postoperative BMI between them ( Ftime=4.22 , P<0.05). Conclusion:LPG can be used to the treatment of proximal gastric cancer and adenocarcinoma of esophagogastric junction, with a good safety and short-term efficacy.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may keep patients in a clinically asymptomatic state by blocking cellular innate antiviral immunity, but the molecular mechanism remains unclear. Here, we screened the viral proteins of SARS-CoV-2 and found that the spike (S) protein inhibits the activation of interferon-stimulated genes (ISGs) and even reduces the expression of these genes to below background values. Mechanistically, the S protein interacted with STAT1, STAT2, and IRF9 and impedes the phosphorylation of STAT1/STAT2, thus preventing the formation of the interferon-stimulating gene factor 3 (ISGF3) complex and inhibiting the downstream production of Interferon-stimulated genes (ISGs). Remarkably, we also have found that the inhibitory mechanism of the S protein was conservative among SARS-CoV-2 variants and other human coronaviruses, including SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Truncation studies indicated that the most conserved S2 domain played a major inhibitory role. Altogether, our findings unveil a new mechanism by which SARS-CoV-2 S protein attenuated the hosts antiviral immune response and provide new insights into the pathogenic mechanism of coronavirus.
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Objective:To explore the relationship between the changes of total cholesterol (TC), C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and the degree of false lumen thrombosis after thoracic endovascular aortic repair (TEVAR) and its clinical significance.Methods:A total of 95 patients with aortic dissection admitted to the Affiliated Hospital of Jining Medical College from June 2015 to July 2020 were selected for retrospective study. All patients were treated with TEVAR. According to the disappearance of false lumen detected by computed tomography (CT) angiography six months after operation, 95 patients were divided into complete disappearance group ( n=43) and incomplete disappearance group ( n=52). The levels of plasma TC, CRP and VEGF in the two groups were compared before operation and 1 and 3 months after operation, as well as the degree of false lumen thrombosis. Spearman′s method was used to analyze the relationship between the levels of plasma TC, CRP and VEGF and the degree of postoperative false lumen thrombosis; multivariate logistic regression was used to analyze the factors affecting the disappearance of false lumen after TEVAR; The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the value of each index in predicting the complete disappearance of false lumen. Results:The plasma levels of TC, CRP and VEGF in the complete disappearance group were lower than those in the incomplete disappearance group 1 and 3 months after operation (all P<0.05). The degree of false lumen thrombosis in the complete disappearance group was significantly different from that in the incomplete disappearance group 1 and 3 months after operation (all P<0.05). The plasma levels of TC, CRP and VEGF 1 and 3 months after TEVAR were negatively correlated with the degree of false lumen thrombosis (all P<0.05). Multivariate logistic regression analysis showed that the plasma levels of TC, CRP and VEGF 1 and 3 months after operation were correlated with the disappearance of false lumen (all P<0.05). With the passage of time, the AUC of each index to predict the complete disappearance of false lumen gradually increased. At 3 months after operation, the AUC of TC, CRP, VEGF and combined prediction of the complete disappearance of false lumen were 0.706, 0.899, 0.781 and 0.943, respectively (all P<0.05). Conclusions:The changes of plasma TC, CRP and VEGF levels after TEVAR are related to the degree of false lumen thrombosis and the disappearance of false lumen in patients with aortic dissection. Combined examination of the three can be an effective method to predict the complete disappearance of false lumen.
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Objective:To determine the predictive value of atherogenic index of plasma (AIP) on the long-term prognosis of patients with coronary artery disease (CAD).Methods:A total of 2 500 patients with coronary heart disease who underwent coronary angiography in Affiliated Hospital of Jining Medical University from May 2013 to November 2015 were retrospectively analyzed. According to the AIP value, the subjects were divided into low AIP group (AIP<0.06) and high AIP group (AIP≥0.06). The incidence of major adverse cardiovascular events (MACE) was compared between the two groups. Kaplan-meier method was used to evaluate the MACE-free survival rate, and multivariate Cox survival analysis was used to evaluate the independent predictors of MACE.Results:A total of 2 427 patients were followed up, with a follow-up rate of 97.08% and a median follow-up time of 4.29 years. There were 1 123 cases in the low AIP group and 1 304 cases in the high AIP group, among which 624 patients (25.7%) had MACE. The total incidence of MACE in the high AIP group was higher than that in the low AIP group ( HR=1.43, 95% CI: 1.22-1.68, P<0.01). Kaplan-meier curves showed that the MACE-free survival rate was significantly lower in the high AIP group ( P<0.01). After adjusting for multiple confounding factors, AIP was still associated with the prognosis of CHD patients. Increased AIP (≥0.06) was an independent predictor of MACE in CHD patients within 4 years ( HR=1.34, 95% CI: 1.14-1.58, P<0.01). Conclusions:AIP (≥0.06) was an independent predictor of MACE occurrence in patients with CAD within 4 years. AIP has a certain value in the long-term prognosis of patients with CAD.
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SARS-CoV-2 continued to spread globally along with different variants. Here, we systemically analyzed viral infectivity and immune-resistance of SARS-CoV-2 variants to explore the underlying rationale of viral mutagenesis. We found that the Beta variant harbors both high infectivity and strong immune resistance, while the Delta variant is the most infectious with only a mild immune-escape ability. Remarkably, the Omicron variant is even more immune-resistant than the Beta variant, but its infectivity increases only in Vero E6 cells implying a probable preference for the endocytic pathway. A comprehensive analysis revealed that SARS-CoV-2 spike protein evolved into distinct evolutionary paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance, resulting in a narrow spectrum of the current single-strain vaccine. In light of these findings and the phylogenetic analysis of 2674 SARS-CoV-2 S-protein sequences, we generated a consensus antigen (S6) taking the most frequent mutations as a pan-vaccine against heterogeneous variants. As compared to the ancestry SWT vaccine with significantly declined neutralizations to emerging variants, the S6 vaccine elicits broadly neutralizing antibodies and full protections to a wide range of variants. Our work highlights the importance and feasibility of a universal vaccine strategy to fight against antigen drift of SARS-CoV-2.
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Objective:Using lasso regression analysis to screen out the blood lipid indexes closely related to coronary heart diseaseMethods:The clinical data of 3 062 patients with coronary heart disease who were hospitalized in the Department of Cardiology, Affiliated Hospital of Jining Medical College from May 2013 to November 2015 were retrospectively analyzed.They were divided into control group ( n=2 427) and coronary angiography group ( n=635). R language was used for statistical analysis.Multiple logistic regression models were established for indicators of blood lipid related to CAD, and their multicollinearity severity was assessed.LASSO regression was used to screen out the representative lipid parameters in the CAD prediction model. Results:A total of 3 062 patients were enrolled, including 2 427 patients in coronary heart disease group and 635 patients in control group.The inclusion of lipid parameters into multiple logistic regression model leads to serious multicollinearity.Stepwise regression can only partially reduce multicollinearity severity, while LASSO regression model significantly reduces multicollinearity severity.Low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) were found to be the representative lipid indexes for predicting coronary heart disease by LASSO regression analysis.Conclusion:LASSO regression has advantages in processing multicollinearity data.LASSO regression showed that LDL-C, HDL-C and non-HDL-C were representative lipid indicators for predicting coronary heart disease..
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The upcoming flu season in the northern hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental co-infection of IAV with either pseudotyped or SARS-CoV-2 live virus, we found that IAV pre-infection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAV in vivo. Moreover, such enhancement of SARS-CoV-2 infectivity was not seen with several other viruses probably due to a unique IAV segment as an inducer to elevate ACE2 expression. This study illustrates that IAV has a special nature to aggravate SARS-CoV-2 infection, and prevention of IAV is of great significance during the COVID-19 pandemic.
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Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of coronavirus SARS-CoV-2. Existing direct-acting antiviral (DAA) drugs cannot be applied immediately to new viruses because of virus-specificity, and the development of new DAA drugs from the beginning is not timely for outbreaks. Thus, host-targeting antiviral (HTA) drugs have many advantages to fight against a broad spectrum of viruses, by blocking the viral replication and overcoming the potential viral mutagenesis simultaneously. Herein, we identified two potent inhibitors of DHODH, S312 and S416, with favorable drug-like and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus (H1N1, H3N2, H9N2), Zika virus, Ebola virus, and particularly against the recent novel coronavirus SARS-CoV-2. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knocking-out cells. We also proposed the drug combination of DAA and HTA was a promising strategy for anti-virus treatment and proved that S312 showed more advantageous than Oseltamivir to treat advanced influenza diseases in severely infected animals. Notably, S416 is reported to be the most potent inhibitor with an EC50 of 17nM and SI value >5882 in SARS-CoV-2-infected cells so far. This work demonstrates that both our self-designed candidates and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-repression may have clinical potentials not only to influenza but also to COVID-19 circulating worldwide, no matter such viruses mutate or not.
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Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Subject(s)
Animals , Humans , Mice , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Influenza A virus , Leflunomide , Pharmacology , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus ReplicationABSTRACT
Digestive tract reconstruction after laparoscopic total gastrectomy is one of the difficult problems faced by surgeons. The classical reconstruction method is Roux-en-Y esophagojejunostomy, which is mainly completed by two instruments: linear stapler and tubular stapler. Due to the advantages of wide application range and safety of anastomosis, the tubular stapler is most commonly used in clinical practice. The traditional method of esophagojejunostomy with tubular stapler is end-to-side esophagojejunostomy. Because this method is directly transplanted from open surgery, there are many difficulties in the actual operation. Semi end to end esophagojejunostomy is an improved reconstruction method with tubular stapler. It is easy to operate and has less complications. It is the optimal choice for digestive tract reconstruction after laparoscopic total gastrectomy. With the help of 4K laparoscopic system, the operation is more accurate. The authors summarize key points of digestive tract reconstruction with tubular stapler after 4K laparoscopic total gastrectomy.
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Minimally invasive surgery experienced a rapid development in the past thirty years, of which the laparoscopy has been widely used in gastrointestinal surgery. Lymph node dissection is one of the difficulties of laparoscopic radical resection of gastric cancer. The lymph node dissection along the left gastroepiploic vessels is a difficult part, which usually causes bleeding and splenic injury. This article mainly introduce the indications, contraindications, surgical preparations, the difficulties and techniques during the lymph nodes dissection when the operator stood on the left side of the patients, and perioperative complications of lymph nodes dissection along the left gastroepiploic vessels.
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The technique of lymph node dissection in laparoscopic radical total gastrectomy is very difficult. The surgeons should strictly grasp the operation indications, cooperate closely with the team during the operation, standardize the extent of lymph node dissection according to the radical resection stan-dards, and realize standardized and accurate operation with the help of 4K laparoscopic system, so as to reduce the occurrence of complications.
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Objective:To investigate the clinical value of semi-end-to-end esophagojejunal anastomosis versus side-to-side esophagojejunal anastomosis in laparoscopic total radical gastrectomy for adenocarcinoma of esophagogastric junction.Methods:The retrospective cohort study was conducted. The clinical data of 85 patients with adenocarcinoma of esophagogastric junction who were admitted to the First Hospital Affiliated to Army Medical University from January 2016 to January 2019 were collected. There were 65 males and 20 females, aged (58±10)years, with a range of 36 to 84 years. Of the 85 patients, 46 patients undergoing laparoscopic total gastrectomy+ D 2 lymphadenectomy+ semi-end-to-end esophagojejunal anastomosis were allocated into semi-end-to-end anastomosis group, and 39 patients undergoing laparoscopic radical total gastrectomy+ D 2 lymphadenectomy+ side-to-side esophagojejunal anastomosis were allocated into side-to-side anastomosis group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was performed by outpatient examination and telephone interview to detect the survival, anastomotic stenosis and tumor recurrence at postoperative one year up to January 2020. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was analyzed using the t test. Count data were expressed as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ranked data was analyzed using the nonparametric rank sum test. Results:(1) Surgical situations: patients of two groups successfully underwent laparoscopic total gastrectomy with D 2 lymph node dissection, without conversion to open surgery or perioperative death. The proximal length between tumor and surgical margin, time of esophagojejunal anastomosis, length of auxiliary incision were (2.3±0.9)cm, (32±3)minutes, (7.5±1.6)cm for the semi-end-to-end anastomosis group, respectively, versus (1.6±1.0)cm, (42±5)minutes, (4.8±1.2)cm for the side-to-side anastomosis group, showing significant differences between the two groups ( t=3.334, 10.177, 8.734, P<0.05). During the esophageal jejunal anastomosis, one patient in the side-to-side anastomosis group had proximal jejunum punctured by a linear cutting stapler resulting in jejunal rupture. The ruptured segment of jejunum was resected and the mesojejunum was freed to perform side-to-side anastomosis. (2) Postoperative situations: there was 1 and 7 patients with postoperative anastomotic bleeding in the semi-end-to-end anastomosis group and side-to-side anastomosis group, respectively, showing a significant difference ( χ2=4.449, P<0.05). Patients with postoperative anastomotic bleeding in the semi-end-to-end anastomosis group and side-to-side anastomosis group were cured after conservative treatment including blood transfusion and endoscopic hemostasis. One patient with esophagojejunal fistula in the side-to-side anastomosis group was cured after conservative treatment including puncture drainage and anti-infective treatment. Two patients with duodenal stump fistula in side-to-side anastomosis group were cured by anti-infection, puncture drainage and nutritional support. Eight patients with pulmonary infection (5 cases in semi-end-to-end anastomosis group and 3 cases in side-to-side anastomosis group) were cured by anti-infection, atomization and expectorant therapy. Three patients with abdominal infection (2 cases in semi-end-to-end anastomosis group and 1 case in side-to-side anastomosis group) were cured by anti-infection and abdominal puncture drainage. One case with incisional infection in semi-end-to-end anastomosis group was cured by dressing change and anti-infective treatment. (3) Follow-up: all the 85 patients were followed up for 1 year. During the follow-up, 3 and 2 patients died in semi-end-to-end anastomosis group and side-to-side anastomosis group, 0 and 2 patients had anastomotic stricture. There was no anastomotic recurrence. Conclusion:In laparoscopic total gastrectomy of adenocarcinoma of esophagogastric junction, semi-end-to-end esophagojejunal anastomosis has the advantages of higher proximal surgical magin from the tumor, shorter anastomosis time, less postoperative anastomotic bleeding, while side-to-side anastomosis anastomosis has shorter length of auxiliary incision.
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Objective:To investigate the short-term outcomes of Da Vinci robotic versus laparoscopic and open surgery for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 404 patients with locally advanced Siewert type Ⅱ and Ⅲ AEG who underwent radical gastrectomy in the First Hospital Affiliated to Army Medical University from January 2009 to April 2019 were collected. There were 331 males and 73 females, aged from 34 to 90 years, with a median age of 62 years. Of the 404 patients, 104 undergoing Da Vinci robotic radical gastrectomy were allocated into robotic group, 205 undergoing laparoscopic radical gastrectomy were allocated into laparoscopic group, and 95 undergoing open radical gastrectomy were allocated into open group. Observation indicators: (1) the propensity score matching conditions and comparison of general data among the three groups after propensity score matching; (2) surgical situations; (3) intraoperative lymph node dissection; (4) postoperative situations; (5) postoperative complications; (6) follow-up. Patients were followed up at postoperative 1 month by outpatient examination and telephone interview to detect survival and severe complications up to June 2019. The propensity score matching was used to perform 1∶2∶1 nearest neighbor matching by SPSS 23.0 and R software 3.6.1 Matchit among the robotic group, laparoscopic group and open group. Measurement data with normal distribution were represented as Mean± SD, and comparison among groups was done using one-way ANOVA analysis. Measurement data with skewed distribution were represented as M (range), and comparison was done using the Kruskal-Wallis H test. Comparison of ordinal data was analyzed using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparison among groups was done using the chi-square test. Results:(1) The propensity score matching conditions and comparison of general data among the three groups after propensity score matching: 312 of 404 patients had successful matching, including 78 in the robotic group, 156 in the laparoscopic group, and 78 in the open group. The age, cases in G1, G2, G3 (histopathological classification) and cases with proximal gastrectomy or total gastrectomy (surgical resection range) before matching were (62.2±1.0)years, 0, 37, 67, 13, 91 in the robotic group, (60.9±8.1)years, 0, 98, 107, 31, 174 in the laparoscopic group, and (58.5±9.8)years, 1, 32, 62, 27, 68 in the open group, showing significant differences among the three groups ( F=4.269, 6.356, χ2=10.416, P<0.05). The above indicators after matching were (61.2±10.8)years, 0, 28, 50, 12, 66 in the robotic group, (60.7±8.0)years, 0, 56, 100, 25, 131 in the laparoscopic group, and (60.7±8.4)years, 0, 25, 53, 18, 60 in the open group, showing no significant difference among the three groups ( F=0.074, 0.379, χ2=2.141, P>0.05). (2) Surgical situations: the surgical time, volume of intraoperative blood loss, length of surgical incision, length of proximal margin after matching were 300.0 minutes(range, 188.0-420.0 minutes), 137.5 mL(range, 50.0-400.0 mL), 6.0 cm(range, 3.0-12.0 cm), 2.5 cm(range, 1.5-5.5 cm) in the robotic group, 276.0 minutes(range, 180.0-400.0 minutes), 150.0 mL(range, 40.0-800.0 mL), 6.0 cm(range, 3.0-12.0 cm), 3.0 cm(range, 1.0-5.0 cm) in the laparoscopic group, and 244.5 minutes(range, 125.0-461.0 minutes), 200.0 mL(range, 55.0-800.0 mL), 20.0 cm(range, 18.0-25.0 cm), 2.0 cm(range, 1.0-5.5 cm) in the open group, showing significant differences among the three groups ( χ2=27.619, 30.069, 179.367, 11.560, P<0.05). (3) Intraoperative lymph node dissection: the number of lymph node dissected, the number of lymph node dissected in the first station, the number of diaphragmatic and periesophageal lymph node dissected were 30.5(range, 10.0-70.0), 18.0(range, 6.0-42.0), 4.0(range, 0-13.0) in the robotic group, 29.0(range, 12.0-79.0), 19.0(range, 6.0-47.0), 5.0(range, 0-15.0) in the laparoscopic group, and 29.0(range, 18.0-58.0), 18.0(range, 12.0-38.0), 5.0(range, 0-8.0) in the open group, showing no significant difference among the three groups ( χ2=3.676, 1.014, 0.827, P>0.05). The number of lymph node dissected in the second station, the number of lymph node dissected in the superior pancreatic region, the number of No.110 lymph node dissected, the number of No.111 lymph node dissected after matching were 9.0(range, 2.0-30.0), 9.0(range, 2.0-30.0), 1.0(range, 0-4.0), 0(range, 0-3.0) in the robotic group, 6.5(range, 0-25.0), 7.0(range, 0-25.0), 0(range, 0-3.0), 0(range, 0-4.0) in the laparoscopic group, and 6.5(range, 0-19.0), 6.5(range, 0-19.0), 0(range, 0-1.0), 0(range, 0-1.0) in the open group, showing significant differences among the three groups ( χ2=19.027, 24.368, 19.236, 11.147, P<0.05). (4) Postoperative situations: the time to first flatus, time to initial out-of-bed activities, duration of postoperative hospital stay, treatment expenses after matching were 3 days(range, 2-5 days), 2 days(range, 1-4 days), 9 days(range, 5-20 days), 10.6×10 4 yuan [range, (5.4-18.0)×10 4 yuan] in the robotic group, 3 days(range, 2-8 days), 2 days(range, 1-7 days), 9 days(range, 6-56 days), 8.6×10 4 yuan[range, (5.7-40.8)×10 4 yuan] in the laparoscopic group, and 4 days(range, 2-10 days), 4 days(range, 2-10 days), 11 days(range, 8-41 days), 8.4×10 4 yuan[range, (5.8-15.2)×10 4 yuan] in the open group, showing significant differences among the three groups ( χ2=28.487, 95.069, 39.443, 83.899, P<0.05). (5) Postoperative complications: the incidence of overall complications, incidence of severe complications (Clavien-Dindo classification ≥grade 3), incidence of gastrointestinal complications, incidence of incisional complications, incidence of respiratory complications, incidence of infection were 21.8%(17/78), 5.1%(4/78), 10.3%(8/78), 1.3%(1/78), 7.7%(6/78), 2.6%(2/78) in the robotic group, 21.8%(34/156), 7.1%(11/156), 5.1%(8/156), 1.3%(2/156), 11.5%(18/156), 3.8%(6/156) in the laparoscopic group, and 29.5%(23/78), 6.4%(5/78), 9.0%(7/78), 2.6%(2/78), 14.1%(11/78), 2.6%(2/78) in the open group, showing no significant difference among the three groups ( χ2=1.913, 0.321, 2.394, 0.866, 1.641, 0.335, P>0.05). (6) Follow-up: 312 patients after propensity score matching were follow up at postoperative 1 month. During the follow-up, 2 cases with severe complications died after discharge. No severe complication such as obstruction of input or output loop, dumping syndrome was found in the other 310 patients. Conclusions:The Da Vinci robotic radical gastrectomy is safe and feasible for locally advanced Siewert type Ⅱ and Ⅲ AEG. Compared with laparoscopic and open radical gastrectomy, Da Vinci robotic radical gastrectomy has more advantages in the number of lymph node dissected in the second station (especially in the superior pancreatic region).
ABSTRACT
Objective To investigate the incidence of postoperative pancreatic fistula (POPF) and its risk factors after radical gastrectomy.Methods The prospective study was conducted.The clinicopathological data of 2 089 patients who underwent radical gastrectomy in 22 medical centers between December 2017 and November 2018 were collected,including 380 in the Zhongshan Hospital of Fudan University,351 in the Renji Hospital of Shanghai Jiaotong University School of Medicine,130 in the Ruijin Hospital of Shanghai Jiaotong University School of Medicine,139 in the Peking University Cancer Hospital,128 in the Fujian Provincial Cancer Hospital,114 in the First Hospital Affiliated to Army Medical University,104 in the First Affiliated Hospital of Nanchang University,104 in the Affiliated Hospital of Qinghai University,103 in the Weifang People's Hospital,102 in the Fujian Medical University Union Hospital,99 in the First Affiliated Hospital of Air Force Medical University,97 in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine,60 in the Hangzhou First People's Hospital Affiliated to Zhejiang University School of Medicine,48 in the Fudan University Shanghai Cancer Center,29 in the First Affiliated Hospital of Xi'an Jiaotong University,26 in the Lishui Municipal Central Hospital,26 in the Guangdong Provincial People's Hospital,23 in the Jiangsu Province Hospital,13 in the First Affiliated Hospital of Sun Yat-Sen University,7 in the Second Hospital of Jilin University,4 in the First Affiliated Hospital of Xinjiang Medical University,2 in the Beijing Chao-Yang Hospital of Capital Medical University.Observation indicators:(1) the incidence of POPF after radical gastrectomy;(2) treatment of grade B POPF after radical gastrectomy;(3) analysis of clinicopathological data;(4) analysis of surgical data;(5) risk factors for grade B POPF after radical gastrectomy.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was analyzed using ANOVA.Count data were described as absolute numbers or percentages,and comparison between groups was analyzed using the chi-square test.Univariate analysis was conducted using the t test or chi-square test based on data excluding missing data of clinicopathological and surgical data.Multivariate analysis was conducted using the Logistic regression model based on factors with P＜0.20 in univariate analysis.Results There were 2 089 patients screened for eligibility,including 1 512 males,576 females and 1 without sex information,aged (62± 11)years.The body mass index (BMI) was (23±3) kg/m2.(1) The incidence of POPF after radical gastrectomy:the total incidence rate of POPF in the 2 089 patients was 20.728％(433/2 089).The incidence rates of biochemical fistula,grade B pancreatic fistula,and grade C pancreatic fistula were 19.627％(410/2 089),1.101％(23/2 089),0,respectively.(2) Treatment of grade B POPF after radical gastrectomy:2 of 23 patients with grade B POPF after radical gastrectomy had drainage tube placed for more than 21 days and received anti-infective therapy.Four of 23 patients with grade B POPF after radical gastrectomy had ascites detected by imaging examination,of which 2 received peritoneal drainage guided by ultrasound,1 received failed puncture drainage,1 received no puncture drainage,and they were given anti-infective therapy.Eleven of 23 patients with grade B POPF after radical gastrectomy had no ascites detected by imaging examinations,and they were given anti-infective therapy and inhibitors of pancreas secretion for clinical manifestation as fever or elevated white blood cells.Six patients with no typical clinical manifestations were given somatostatin to inhibite pancreas secretion and prolonged duration of abdominal drainage tube placement (with a median time of 7 days).All the 23 patients recovered well after treatment,without reoperation.(3) Analysis of clinicopathological data:for the 2 089 patients,BMI,cases with or without neoadjuvant therapy were (23±3) kg/m2,1 487,160 of patients without pancreatic fistula,(23±3)kg/m2,386,22 of patients with biochemical fistula,and (24±3)kg/m2,22,1 of patents with grade B pancreatic fistula,showing significant differences between the three groups (F=5.787,x2 =8.269,P＜0.05).(4) Analysis of surgical data:for the 2 089 patients,cases with open surgery,laparoscopic assisted surgery,totally laparoscopic surgery (surgical method),cases with D1 lymph lode dissection,D2 lymph lode dissection,and other lymph lode dissection (range of lymph lode dissection),cases with no omentectomy,partial omentectomy,and total omentectomy (range of omentectomy),cases with no usage of energy facility,usage of CUSA,LigaSure,LigaSure+CUSA as energy facility,cases with or without biological glue,the number of lymph node dissection were 737,624,292,24,1 580,51,418,834,381,63,1 530,23,16,1 431,201,33±14 of patients without pancreatic fistula,146,189,74,11,389,9,110,171,128,35,359,6,9,378,31,31± 14 of patients with biochemical fistula,and 14,5,4,0,20,3,6,13,4,2,18,1,2,22,1,37±16 of patients with grade B pancreatic fistula,showing significant differences between the three groups (x2=15.578,9.397,15.023,28.245,8.359,F=4.945,P＜ 0.05).(5) Risk factors for grade B POPF after radical gastrectomy:results of univariate analysis showed that usage of energy facility was a related factor for grade B POPF after radical gastrectomy (x2=9.914,P＜0.05).Results of multivariate analysis showed that laparoscopic assisted surgery,combined evisceration,application of LigaSure + CUSA,the number of lymph lode dissection were independent factors for for grade B POPF after radical gastrectomy (odds ratio=0.168,3.922,9.250,1.030,95％ confidence interval:0.036-0.789,1.031-14.919,1.036-82.602,1.001-1.059,P＜0.05).Conclusions The incidence of grade B POPF after radical gastrectomy is relatively low.Laparoscopic assisted surgery,combined evisceration,application of LigaSure + CUSA,and the number of lymph lode dissection are independent risk factors for grade B POPF.Trial Registration:This study was registrated at ClinicalTrial.gov in United States with the registration number of NCT03391687.
ABSTRACT
Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Subject(s)
Animals , Humans , Mice , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Influenza A virus , Leflunomide , Pharmacology , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus ReplicationABSTRACT
Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Subject(s)
Animals , Humans , Mice , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Influenza A virus , Leflunomide , Pharmacology , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus ReplicationABSTRACT
Objective@#To investigate the incidence of postoperative pancreatic fistula (POPF) and its risk factors after radical gastrectomy.@*Methods@#The prospective study was conducted. The clinicopathological data of 2 089 patients who underwent radical gastrectomy in 22 medical centers between December 2017 and November 2018 were collected, including 380 in the Zhongshan Hospital of Fudan University, 351 in the Renji Hospital of Shanghai Jiaotong University School of Medicine, 130 in the Ruijin Hospital of Shanghai Jiaotong University School of Medicine, 139 in the Peking University Cancer Hospital, 128 in the Fujian Provincial Cancer Hospital, 114 in the First Hospital Affiliated to Army Medical University, 104 in the First Affiliated Hospital of Nanchang University, 104 in the Affiliated Hospital of Qinghai University, 103 in the Weifang People′s Hospital, 102 in the Fujian Medical University Union Hospital, 99 in the First Affiliated Hospital of Air Force Medical University, 97 in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, 60 in the Hangzhou First People′s Hospital Affiliated to Zhejiang University School of Medicine, 48 in the Fudan University Shanghai Cancer Center, 29 in the First Affiliated Hospital of Xi′an Jiaotong University, 26 in the Lishui Municipal Central Hospital, 26 in the Guangdong Provincial People′s Hospital, 23 in the Jiangsu Province Hospital, 13 in the First Affiliated Hospital of Sun Yat-Sen University, 7 in the Second Hospital of Jilin University, 4 in the First Affiliated Hospital of Xinjiang Medical University, 2 in the Beijing Chao-Yang Hospital of Capital Medical University. Observation indicators: (1) the incidence of POPF after radical gastrectomy; (2) treatment of grade B POPF after radical gastrectomy; (3) analysis of clinicopathological data; (4) analysis of surgical data; (5) risk factors for grade B POPF after radical gastrectomy. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using ANOVA. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the t test or chi-square test based on data excluding missing data of clinico-pathological and surgical data. Multivariate analysis was conducted using the Logistic regression model based on factors with P<0.20 in univariate analysis.@*Results@#There were 2 089 patients screened for eligibility, including 1 512 males, 576 females and 1 without sex information, aged (62±11)years. The body mass index (BMI) was (23±3)kg/m2. (1) The incidence of POPF after radical gastrectomy: the total incidence rate of POPF in the 2 089 patients was 20.728%(433/2 089). The incidence rates of biochemical fistula, grade B pancreatic fistula, and grade C pancreatic fistula were 19.627%(410/2 089), 1.101%(23/2 089), 0, respectively. (2) Treatment of grade B POPF after radical gastrectomy: 2 of 23 patients with grade B POPF after radical gastrectomy had drainage tube placed for more than 21 days and received anti-infective therapy. Four of 23 patients with grade B POPF after radical gastrectomy had ascites detected by imaging examination, of which 2 received peritoneal drainage guided by ultrasound, 1 received failed puncture drainage, 1 received no puncture drainage, and they were given anti-infective therapy. Eleven of 23 patients with grade B POPF after radical gastrectomy had no ascites detected by imaging examinations, and they were given anti-infective therapy and inhibitors of pancreas secretion for clinical manifestation as fever or elevated white blood cells. Six patients with no typical clinical manifestations were given somatostatin to inhibite pancreas secretion and prolonged duration of abdominal drainage tube placement (with a median time of 7 days). All the 23 patients recovered well after treatment, without reoperation. (3) Analysis of clinicopathological data: for the 2 089 patients, BMI, cases with or without neoadjuvant therapy were (23±3)kg/m2, 1 487, 160 of patients without pancreatic fistula, (23±3)kg/m2, 386, 22 of patients with biochemical fistula, and (24±3)kg/m2, 22, 1 of patents with grade B pancreatic fistula, showing significant differences between the three groups (F=5.787, χ2=8.269, P<0.05). (4) Analysis of surgical data: for the 2 089 patients, cases with open surgery, laparoscopic assisted surgery, totally laparoscopic surgery (surgical method), cases with D1 lymph lode dissection, D2 lymph lode dissection, and other lymph lode dissection (range of lymph lode dissection), cases with no omentectomy, partial omentectomy, and total omentectomy (range of omentectomy), cases with no usage of energy facility, usage of CUSA, LigaSure, LigaSure+ CUSA as energy facility, cases with or without biological glue, the number of lymph node dissection were 737, 624, 292, 24, 1 580, 51, 418, 834, 381, 63, 1 530, 23, 16, 1 431, 201, 33±14 of patients without pancreatic fistula, 146, 189, 74, 11, 389, 9, 110, 171, 128, 35, 359, 6, 9, 378, 31, 31±14 of patients with biochemical fistula, and 14, 5, 4, 0, 20, 3, 6, 13, 4, 2, 18, 1, 2, 22, 1, 37±16 of patients with grade B pancreatic fistula, showing significant differences between the three groups (χ2=15.578, 9.397, 15.023, 28.245, 8.359, F=4.945, P<0.05). (5) Risk factors for grade B POPF after radical gastrectomy: results of univariate analysis showed that usage of energy facility was a related factor for grade B POPF after radical gastrectomy (χ2=9.914, P<0.05). Results of multivariate analysis showed that laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, the number of lymph lode dissection were independent factors for for grade B POPF after radical gastrectomy (odds ratio=0.168, 3.922, 9.250, 1.030, 95% confidence interval: 0.036-0.789, 1.031-14.919, 1.036-82.602, 1.001-1.059, P<0.05).@*Conclusions@#The incidence of grade B POPF after radical gastrectomy is relatively low. Laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, and the number of lymph lode dissection are independent risk factors for grade B POPF. Trial Registration: This study was registrated at ClinicalTrial.gov in United States with the registration number of NCT03391687.
ABSTRACT
Digestive tract reconstruction after laparoscopic total gastrectomy is one of the difficult problems faced by surgeons. The classical reconstruction method is Roux-en-Y esophagojejunostomy, which is mainly completed by two instruments: linear stapler and tubular stapler. Due to the advantages of wide application range and safety of anastomosis, the tubular stapler is most commonly used in clinical practice. The traditional method of esophagojejunostomy with tubular stapler is end-to-side esophagojejunostomy. Because this method is directly transplanted from open surgery, there are many difficulties in the actual operation. Semi end to end esophagojejunostomy is an improved reconstruction method with tubular stapler. It is easy to operate and has less complications. It is the optimal choice for digestive tract reconstruction after laparoscopic total gastrectomy. With the help of 4K laparoscopic system, the operation is more accurate. The authors summarize key points of digestive tract reconstruction with tubular stapler after 4K laparoscopic total gastrectomy.
