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IMPORTANCE: Splenic hilar lymphadenectomy has been recommended for locally advanced proximal gastric cancer (APGC) involving the greater curvature. However, it is unclear whether laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) is associated with a long-term survival benefit for APGC without greater curvature invasion. OBJECTIVE: To present the 5-year follow-up data from a randomized clinical trial that compared laparoscopic total gastrectomy (D2 group) with D2 plus LSPSHL (D2 + No. 10 group) among patients with resectable APGC. DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc secondary analysis of a randomized clinical trial that enrolled 536 patients with potentially resectable APGC (cT2-4a, N0 or N+, and M0) without greater curvature invasion from January 5, 2015, to October 10, 2018. All patients were tracked for at least 5 years. The final follow-up was on October 30, 2023. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to the D2 + No. 10 or D2 groups. MAIN OUTCOMES AND MEASURES: The 5-year disease-free survival (DFS) and overall survival (OS) rates were measured. Recurrence patterns and causes of death were compared. RESULTS: A total of 526 patients (392 men [74.5%]; mean [SD] age, 60.6 [9.6] years) were included in the modified intent-to-treat analysis, with 263 patients in each group. The 5-year DFS rate was 63.9% (95% CI, 58.1%-69.7%) for the D2 + No. 10 group and 55.1% (95% CI, 49.1%-61.1%) for the D2 group (log-rank P = .04). A statistically significant difference was observed in the 5-year OS between the D2 + No. 10 group and the D2 group (66.2% [95% CI, 60.4%-71.9%] vs 57.4% [95% CI, 51.4%-63.4%]; log-rank P = .03). The No. 10 lymph node exhibited a therapeutic value index (TVI) of 6.5, surpassing that of Nos. 8a (TVI, 3.0), 11 (TVI, 5.8), and 12a (TVI, 0.8). A total of 86 patients in the D2 + No. 10 group (cumulative incidence, 32.7%) and 111 patients in the D2 group (cumulative incidence, 42.2%) experienced recurrence (hazard ratio, 0.72; 95% CI, 0.54-0.95; P = .02). The multivariable competing risk regression model demonstrated that D2 + No. 10 remained an independent protective factor for a lower 5-year cumulative recurrence rate after surgery (hazard ratio, 0.75; 95% CI, 0.56-1.00; P = .05). There was a significant difference in the 5-year cumulative recurrence rate at the No. 10 lymph node area between the 2 groups (D2 + No. 10 group vs D2 group: 0% vs 2.3% [n = 6]; P = .01). CONCLUSIONS: This post hoc secondary analysis of a randomized clinical trial found that laparoscopic total gastrectomy with LSPSHL can improve the prognosis and reduce recurrence for APGC without greater curvature invasion. Future multicenter studies are warranted to validate these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02333721

Background: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. Methods: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. Results: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20–50) vs. 35 (30–59) mL, median difference (95%CI) − 5 (− 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) − 1.19 (− 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II–III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5–32.5) vs. 32 (27–38.5) days, median difference (95%CI) − 3 (− 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. Conclusion: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2.

Objective: Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC. Methods: Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression. Results: In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P< 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P< 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P< 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort. Conclusion: mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC.

Background: Textbook outcome (TO) has been widely employed as a comprehensive indicator to assess the short-term prognosis of patients with cancer. Preoperative malnutrition is a potential risk factor for adverse surgical outcomes in patients with gastric cancer (GC). This study aimed to compare the TO between robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG) in malnourished patients with GC. Methods: According to the diagnostic consensus of malnutrition proposed by Global Leadership Initiative on Malnutrition (GLIM) and Nutrition Risk Index (NRI), 895 malnourished patients with GC who underwent RAG (n= 115) or LAG (n= 780) at a tertiary referral hospital between January 2016 and May 2021 were included in the propensity score matching (PSM, 1:2) analysis. Results: After PSM, no significant differences in clinicopathological characteristics were observed between the RAG (n= 97) and LAG (n= 194) groups. The RAG group had significantly higher operative time and lymph nodes harvested, as well as significantly lower blood loss and hospital stay time compared to the LAG group. More patients in the RAG achieved TO. Logistic regression analysis revealed that RAG was an independent protective factor for achieving TO. There were more adjuvant chemotherapy (AC) cycles in the RAG group than in the LAG group. After one year of surgery, a higher percentage of patients (36.7% vs. 22.8%; P< 0.05) in the RAG group recovered from malnutrition compared to the LAG group. Conclusions: For malnourished patients with GC, RAG performed by experienced surgeons can achieved a higher rate of TO than those of LAG, which directly contributed to better AC compliance and a faster restoration of nutritional status.

Background: Surgical quality control is a crucial determinant of evaluating the tumor efficacy. Objective: To assess the ClassIntra grade for quality control and oncological outcomes of robotic radical surgery for gastric cancer (GC). Methods: Data of patients undergoing robotic radical surgery for GC at a high-volume center were retrospectively analyzed. Patients were categorized into two groups, the intraoperative adverse event (iAE) group and the non-iAE group, based on the occurrence of intraoperative adverse events. The iAEs were further classified into five sublevels (ranging from I to V according to severity) based on the ClassIntra grade. Surgical performance was assessed using the Objective Structured Assessment of Technical Skill (OSATS) and the General Error Reporting Tool. Results: This study included 366 patients (iAE group: n= 72 [19.7%] and non-iAE group: n= 294 [80.3%]). The proportion of ClassIntra grade II patients was the highest in the iAE group (54.2%). In total and distal gastrectomies, iAEs occurred most frequently in the suprapancreatic area (50.0% and 54.8%, respectively). In total gastrectomy, grade IV iAEs were most common during lymph node dissection in the splenic hilum area (once for bleeding [grade IV] and once for injury [grade IV]). The overall survival (OS) and disease-free survival of the non-iAE group were significantly better than those of the iAE group (Log rank P< 0.001). Uni- and multi-variate analyses showed that iAEs were key prognostic indicators, independent of tumor stage and adjuvant chemotherapy (P< 0.001). Conclusion: iAEs in patients who underwent robotic radical gastrectomy significantly correlated with the occurrence of postoperative complications and a poor long-term prognosis. Therefore, utilization and inclusion of ClassIntra grading as a crucial surgical quality control and prognostic indicator in the routine surgical quality evaluation system are recommended.

Importance: It is largely unclear whether robotic distal gastrectomy (RDG) is cost-effective for locally advanced gastric cancer (LAGC). Objective: To evaluate the cost-effectiveness of RDG, laparoscopic distal gastrectomy (LDG), and open distal gastrectomy (ODG) for patients with LAGC. Design, setting, and participants: Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. A decision-analytic model was constructed to evaluate the cost-effectiveness of RDG, LDG, and ODG. Exposures: RDG, LDG, and ODG. Main outcomes and measures: Incremental cost-effectiveness ratio (ICER) and quality-adjusted life year (QALY). Results: This pooled analysis of two randomized controlled trials included 449 patients: 117, 254, and 78 patients in the RDG, LDG, and ODG groups, respectively. After IPTW, RDG demonstrated its priority in terms of less blood loss, postoperative length, and complication rate (all P< 0.05). RDG also showed higher QOL with more cost, representing an ICER of $85,739.73 per QALY and $42,189.53 per QALY compared to LDG and ODG, respectively. In probabilistic sensitivity analysis, RDG achieved the best cost-effectiveness for patients with LAGC only when the willingness-to-pay threshold was > $85,739.73 per QALY, which significantly exceeded 3 times Chinese per capita GDP. Furthermore, one of the most important factors was the indirect costs of robotic surgery in terms of the cost-effectiveness of RDG compared to that of LDG or ODG. Conclusions and relevance: Although improved short-term outcomes and QOL were seen in patients underwent RDG, the economic burden should be considered in the clinical decision-making regarding robotic surgery use for patients with LAGC. Our findings may vary in different health care settings and affordability.

Background: Laparoscopic technique has been increasingly used in gastrectomy, but the safety and feasibility of the laparoscopic total gastrectomy (LTG) for advanced proximal gastric cancer (PGC) after neoadjuvant chemotherapy (NAC) is unclear. Methods: A retrospective analysis of 146 patients who received NAC followed by radical total gastrectomy at Fujian Medical University Union Hospital from January 2008 to December 2018 was performed. The primary endpoints were long-term outcomes. Results: The patients were divided into two groups: 89 were in the LTG group and 57 were in the open total gastrectomy (OTG) group. The LTG group had a significantly shorter operative time (median 173 min vs. 215 min, p< 0.001), less intraoperative bleeding (62 ml vs. 135 ml, p< 0.001), higher total lymph node (LN) dissections (36 vs 31, p= 0.043), and higher total chemotherapy cycle completion rate (≥ 8 cycles) (37.1% vs. 19.7%, p= 0.027) than OTG. The 3-year overall survival (OS) of the LTG group was significantly higher than that of the OTG group (60.7% vs. 35%, p= 0.0013). Survival with inverse probability weighting(IPW) correction for Lauren type, ypTNM stage, NAC schemes and the times at which the surgery was performed showed that there was no significant difference in OS between the two groups (p= 0.463). Postoperative complications (25.8% vs. 33.3%, p= 0.215) and recurrence-free survival (RFS) (p= 0.561) between the LTG and OTG groups were also comparable. Conclusion: In experienced gastric cancer surgery centers, LTG is recommended as the preferred option for such patients who performed NAC, owing to its long-term survival is not inferior to OTG, and it offers less intraoperative bleeding, better chemotherapy tolerance than conventional open surgery.

IMPORTANCE: The survival benefit of laparoscopic total gastrectomy combined with spleen-preserving splenic hilar lymphadenectomy (LSTG) for locally advanced proximal gastric cancer (APGC) without invasion into the greater curvature remains uncertain. OBJECTIVE: To compare the long-term and short-term efficacy of LSTG (D2 + No. 10 group) and conventional laparoscopic total gastrectomy (D2 group) for patients with APGC that has not invaded the greater curvature. DESIGN, SETTING, AND PARTICIPANTS: In this open-label, prospective randomized clinical trial, a total of 536 patients with clinical stage cT2 to 4a/N0 to 3/M0 APGC without invasion into the greater curvature were enrolled from January 2015 to October 2018. The final follow-up was on October 31, 2021. Data were analyzed from December 2021 to February 2022. INTERVENTIONS: Eligible patients were randomized to the D2 + No. 10 group or the D2 group. MAIN OUTCOMES AND MEASURES: The primary outcome was 3-year disease-free survival (DFS). The secondary outcomes were 3-year overall survival (OS) and morbidity and mortality within 30 days after surgery. RESULTS: Of 526 included patients, 392 (74.5%) were men, and the mean (SD) age was 60.6 (9.6) years. A total of 263 patients were included in the D2 + No. 10 group, and 263 were included in the D2 group. The 3-year DFS was 70.3% (95% CI, 64.8-75.8) for the D2 + No. 10 group and 64.3% (95% CI, 58.4-70.2; P = .11) for the D2 group, and the 3-year OS in the D2 + No. 10 group was better than that in the D2 group (75.7% [95% CI, 70.6-80.8] vs 66.5% [95% CI, 60.8-72.2]; P = .02). Multivariate analysis revealed that splenic hilar lymphadenectomy was not an independent protective factor for DFS (hazard ratio [HR], 0.86; 95% CI, 0.63-1.16) or OS (HR, 0.81; 95% CI, 0.59-1.12). Stratification analysis showed that patients with advanced posterior gastric cancer in the D2 + No. 10 group had better 3-year DFS (92.9% vs 39.3%; P < .001) and OS (92.9% vs 42.9%; P < .001) than those in the D2 group. Multivariate analysis confirmed that patients with advanced posterior gastric cancer could have the survival benefit from No. 10 lymph node dissection (DFS: HR, 0.10; 95% CI, 0.02-0.46; OS: HR, 0.12; 95% CI, 0.03-0.52). CONCLUSIONS AND RELEVANCE: Although LSTG could not significantly improve the 3-year DFS of patients with APGC without invasion into the greater curvature, patients with APGC located posterior gastric wall may benefit from LSTG. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02333721

ObjectiveGastric cancer (GC) ranks fifth in incidence and fourth for mortality worldwide. The response to immune checkpoint blockade (ICB) therapy in GC is heterogeneous due to tumour-intrinsic and acquired immunotherapy resistance. We developed an immunophenotype-based subtyping of human GC based on immune cells infiltration to develop a novel treatment option.DesignA algorithm was developed to reclassify GC into immune inflamed, excluded and desert subtypes. Bioinformatics, human and mouse GC cell lines, syngeneic murine gastric tumour model, and CTLA4 blockade were used to investigate the immunotherapeutic effects by restricting receptor tyrosine kinase (RTK) signalling in immune desert (ICB-resistant) type GC.ResultsOur algorithm restratified subtypes of human GC in public databases and showed that immune desert-type and excluded-type tumours are ICB-resistant compared with immune-inflamed GC. Moreover, epithelial-mesenchymal transition (EMT) signalling was highly enriched in immune desert-type GC, and syngeneic murine tumours exhibiting mesenchymal-like, compared with epithelial-like, properties are T cell-excluded and resistant to CTLA4 blockade. Our analysis further identified a panel of RTKs as potential druggable targets in the immune desert-type GC. Dovitinib, an inhibitor of multiple RTKs, strikingly repressed EMT programming in mesenchymal-like immune desert syngeneic GC models. Dovitinib activated the tumour-intrinsic SNAI1/2-IFN-γ signalling axis and impeded the EMT programme, converting immune desert-type tumours to immune inflamed-type tumours, sensitising these mesenchymal-like ‘cold’ tumours to CTLA4 blockade.ConclusionOur findings identified potential druggable targets relevant to patient groups, especially for refractory immune desert-type/ ‘cold’ GC. Dovitinib, an RTK inhibitor, sensitised desert-type immune-cold GC to CTLA4 blockade by restricting EMT and recruiting T cells.

Objective: To assess the effect of preoperative sarcopenia on the short-term and long-term outcomes in older patients with locally advanced gastric cancer (LAGC). Methods: Clinicopathological data of older patients with LAGC who underwent radical surgery were retrospectively analyzed. Sarcopenia was defined as a skeletal muscle index of less than 36.4 cm2/m2for men and less than 28.4 cm2/m2for women. Comparing the postoperative complications and survival between sarcopenia and non-sarcopenia groups using multicenter data. Results: A total of 406 older patients with LAGC were included in the analysis, including 145 (35.7%) with sarcopenia and 261 (64.3%) with non-sarcopenia. Multivariate logistic regression analysis showed that sarcopenia was an independent risk factor for postoperative complications with CD grade ≥ II (OR 1.616; P< 0.05). Kaplan–Meier survival curve analysis showed that the 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) in the sarcopenia group were lower than those in the non-sarcopenia group (Pboth < 0.05). Multivariate Cox regression analyses showed that sarcopenia was an independent prognostic factor for 5-year OS and RFS (Pboth < 0.05). The 5-year recurrence rate in the sarcopenia group was 57.2%, which was significantly higher than that in the non-sarcopenia group (46.4%; P= 0.036). Recurrence pattern analysis showed that the incidence of distant metastases in patients with sarcopenia (42.8%) was significantly higher than non-sarcopenia (31.4%; P= 0.022). Conclusion: Sarcopenia serves as a valuable predictor of both short-term and long-term outcomes in older patients with LAGC. Therefore, the significance of assessing preoperative nutritional status and implementing thorough postoperative follow-up for older LAGC patients with sarcopenia should be emphasized.

Objective: There is insufficient evidence to evaluate the long-term outcomes of robotic radical gastrectomy. The aim of this study was to compare the radical results and long-term outcomes of robotic and laparoscopic radical gastrectomy. Methods: We prospectively collected and retrospectively analyzed the general clinicopathological data of gastric cancer patients treated with robotic radical gastrectomy (RG) and laparoscopic radical gastrectomy (LG) from July 2016 to July 2018 at Fujian Medical University Union Hospital. The RG cohort was matched 1:3 with the LG cohort by using propensity score matching (PSM). The primary endpoints of the study were 3-year overall survival (OS) and 3-year relapse-free survival (RFS). Results: The study included 221 patients treated with RG and 1106 patients treated with LG for gastric cancer. After PSM, 211 patients were included in the RG cohort, and 663 patients were included in the LG cohort. The 3-year OS rate was 81.0% in the robotic cohort and 79.3% in the laparoscopic cohort (log-rank test, P= 0.516). The 3-year RFS rate was 78.7% in the robotic cohort and 75.6% in the laparoscopic cohort (log-rank test, P= 0.600). In the subgroup analyses, no significant differences were noted between the RG and LG cohorts in terms of 3-year OS and 3-year RFS (all P> 0.05). The therapeutic value index of each lymph node station dissection in the robotic cohort was comparable to that in the laparoscopic cohort. Conclusion: Robotic radical gastrectomy can achieve radical results and long-term outcomes comparable to laparoscopic surgery, and further multicenter prospective studies can be conducted to assess the clinical efficacy of robotic radical gastrectomy.

Background: It remains inconclusive whether laparoscopic gastrectomy (LG) has better long-term outcomes when compared with open gastrectomy (OG) for elderly gastric cancer (EGC). We attempted to explore the influence of the immune prognostic index (IPI) on the prognosis of EGCs treated by LG or OG to identify a population among EGC who may benefit from LG. Methods: We included 1539 EGCs treated with radical gastrectomy from January 2007 to December 2016. Propensity score matching was applied at a ratio of 1:1 to compare the LG and OG groups. The IPI based on dNLR ≥ cut-off value (dNLR) and sLDH ≥ cut-off value (sLDH) was developed, characterizing two groups (IPI = 0, good, 0 factors; IPI = 1, poor, 1 or 2 factors). Results: Of the 528 EGCs (LG: 264 and OG: 264), 271 were in the IPI = 0 group, and 257 were in the IPI = 1 group. In the entire cohort, the IPI = 0 group was associated with good 5-year overall survival (OS) (p= 0.001) and progression-free survival (PFS) (p= 0.003) compared to the IPI = 1 group; no significant differences in 5-year OS and PFS between the LG and OG groups were observed. In the IPI = 1 cohort, there was no significant difference in OS or PFS between the LG and OG groups across all tumor stages. However, in the IPI = 0 cohort, LG was associated with longer OS (p= 0.015) and PFS (p= 0.018) than OG in stage II EGC, but not in stage I or III EGC. Multivariate analysis showed that IPI = 0 was an independent protective factor for stage II EGC receiving LG, but not for those receiving OG. Conclusion: The IPI is related to the long-term prognosis of EGC. Compared with OG, LG may improve the 5-year survival rate of stage II EGC with a good IPI score. This hypothesis needs to be further confirmed by prospective studies.

Background: The oncologic efficacy of laparoscopic versus open surgery for advanced distal gastric cancer (ADGC) beyond 3 years after surgery remain obscure. Methods: A total of 1256 patients with ADGC at two teaching institutions in China from April 2007 to December 2014 were enrolled. The general data of the two groups were identified to enable rigorous estimation of propensity scores. Restricted mean survival time (RMST) and Landmark analysis was used to compare survival. Results: After matching 461 patients each in the open distal gastrectomy (ODG) and laparoscopic distal gastrectomy (LDG) groups, they were included into analysis. The 3- and 5-year overall survival (OS) and disease-free survival were comparable in two groups. RMST-stratified analysis showed that the 3-year RMST of ODG group was similar to that of LDG group in patients with cT4a (− 1.38 years, p= 0.163) or with cT4a and tumor size > 5 cm, whereas the 5-year RMST had significant differences between groups in cT4a patients(− 8.36 years, P= 0.005) or cT4a and tumor size > 5 cm patients(4.67 years, P= 0.042). In patients with cT4a and tumors > 5 cm, the number of peritoneal recurrences was significantly fewer in the ODG group than in the LDG group (4 vs. 17, P= 0.033), and the peritoneal recurrence time and multiple-site recurrence time were both later in the ODG group. Conclusion: By reducing recurrence, ODG achieves a better survival for GC patients with serous infiltration and tumors larger than 5 cm beyond 3 years after surgery. The present findings can serve as a reference for surgical options and the setting of follow-up time point for clinical studies.

We have demonstrated that CDK5RAP3 exerts a tumour suppressor effect in gastric cancer, but its role in regulating tumour-associated macrophages (TAMs) has not yet been reported. Here, we show that CDK5RAP3 is related to the infiltration and polarization of macrophages. It inhibits the polarization of TAMs to M2 macrophages and promotes the polarization of the M1 phenotype. CDK5RAP3 reduces the recruitment of circulating monocytes to infiltrate tumour tissue by inhibiting the CCL2/CCR2 axis in gastric cancer. Blocking CCR2 reduces the growth of xenograft tumours and the infiltration of monocytes. CDK5RAP3 inhibits the nuclear transcription of NF-κB, thereby reducing the secretion of the cytokines IL4 and IL10 and blocking the polarization of M2 macrophages. In addition, the absence of CDK5RAP3 in gastric cancer cells allows macrophages to secrete more MMP2 to promote the epithelial-mesenchymal transition (EMT) process of gastric cancer cells, thereby enhancing the invasion and migration ability. Our results imply that CDK5RAP3 may be involved in the regulation of immune activity in the tumour microenvironment and is expected to become a potential immunotherapy target for gastric cancer.

Objective: To investigate the effect of intraoperative lymph node (LN) dissection and postoperative adjuvant chemotherapy on the overall survival (OS) of gastric cancer (GC) patients and their reciprocity. Methods: LN noncompliance was defined as the absence of more than one LN station, as described in the protocol for D2 lymphadenectomy in the Japanese Gastric Cancer Association. The definition of adjuvant chemotherapy (AC) noncompliance was that the chemotherapy planned dose does not meet the requirements. Results: Kaplan–Meier survival curves showed that the OS of patients with major LN noncompliance was significantly lower than that of patients with nonmajor LN noncompliance, and the OS of AC noncompliance patients was significantly lower than that of AC compliance patients. If there was nonmajor LN noncompliance during surgery, the OS of patients with AC compliance was significantly higher than that of patients with AC noncompliance (P= 0.035). In the case of major LN noncompliance during surgery, there was no statistically significant difference in OS between those with AC compliance and those with AC noncompliance (P = 0.682). Multivariate Cox regression analysis including AC noncompliance indicated that major LN noncompliance was an independent prognostic factor for poor OS (P= 0.012), while AC noncompliance was not an independent prognostic factor for OS (P= 0.609). Conclusion: Adequate lymph node dissection and adjuvant chemotherapy are both key steps to improve the awful prognosis of GC patients. Adjuvant chemotherapy may fail to remedy the poor prognosis caused by major LN noncompliance.

Background: Robotic surgery may be advantageous for complex surgery. We aimed to compare the intraoperative and postoperative short-term outcomes of spleen-preserving splenic hilar lymphadenectomy (SPSHL) during robotic and laparoscopic total gastrectomy. Methods: From July 2016 to December 2020, the clinicopathological data of 115 patients who underwent robotic total gastrectomy combined with robotic SPSHL (RSPSHL) and 697 patients who underwent laparoscopic total gastrectomy combined with laparoscopic SPSHL (LSPSHL) were retrospectively analyzed. A 1:2 ratio propensity score matching (PSM) was used to balance the differences between the two groups to compare their outcomes. The Generic Error Rating Tool was used to evaluate the technical performance. Results: After PSM, the baseline preoperative characteristics of the 115 patients in the RSPSHL and 230 patients in the LSPSHL groups were balanced. The dissection time of the region of the splenic artery trunk (5.4 ± 1.9 min vs. 7.8 ± 3.6 min, P< 0.001), the estimated blood loss during SPSHL (9.6 ± 4.8 ml vs. 14.9 ± 7.8 ml, P< 0.001), and the average number of intraoperative technical errors during SPSHL (15.1 ± 3.4 times/case vs. 20.7 ± 4.3 times/case, P< 0.001) were significantly lower in the RSPSHL group than in the LSPSHL group. The RSPSHL group showed higher dissection rates of No. 10 (78.3% vs. 70.0%, P= 0.104) and No. 11d (54.8% vs. 40.4%, P= 0.012) lymph nodes and significantly improved postoperative recovery results in terms of times to ambulation, first flatus, and first intake (P< 0.05). The splenectomy rates of the two groups were similar (1.7% vs. 0.4%, P= 0.539), and there was no significant difference in morbidity and mortality within postoperative 30 days (13.0% vs. 15.2%, P= 0.589). Conclusion: Compared to LSPSHL, RSPSHL has more advantages in terms of surgical qualities and postoperative recovery process with similar morbidity and mortality. For complex SPSHL, robotic surgery may be a better choice.

Background: Due to lacking evidence for confirming the efficacy of performing laparoscopic surgery for locally advanced gastric cancer (LAGC). Therefore, this study aimed to compare the static and dynamic failure patterns after laparoscopic gastrectomy (LG) and open gastrectomy (OG) in LAGC. Methods: A total of 1792 LAGC patients who underwent radical resection between January 2010 and January 2017 were divided into the LG group (n= 1557) and the OG group (n= 235). Propensity score matching was performed to balance the two groups. Dynamic hazard rates of failure were calculated using the hazard function. Early and late failure were defined as failure occurring before and after 2 years since surgery, respectively. Results: A total of 1175 patients with LAGC were included after matching (LG group, n= 940; OG, n= 235). The failure rate of the whole cohort was 43.2% (508/1175), accounting for 41.4% (389/940) and 50.6% (119/235) in the LG and OG groups, respectively. Although the two groups showed no significant differences in failure rate for any failure type, landmark analysis showed a lower early distant recurrence rate in the stage IIa–IIIb subgroup of the LG group (OG versus LG: 30.3% versus 21.1%, P= 0.004). The dynamic hazard rate peaked at 9.4 months (peak rate = 0.0186) before gradually declining. In stage IIa–IIIb patients, the hazard rate of the OG group remained significantly higher than that of the LG group within the first 2 years in terms of distant recurrence (peak rate: OG versus LG, 0.0091 versus 0.0055). Conclusion: Given the differences in early failure between LG and OG, more intensive surveillance for distant recurrence within the first 2 years should be considered for patients with stage IIa–IIIb after OG.

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The poor prognosis of gastric cancer (GC) results largely from metastasis and chemotherapy resistance. Toward novel therapeutic strategies that target or evade these phenomena, we evaluated the function of the transcriptional regulator transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) in GC cells, including stem-like cells. In this study, the correlation of expression of TBL1XR1 and clinical features and GC patients’ outcomes was evaluated. Knockdown or exogenous expression of TBL1XR1 was combined with in vitro (2D and 3D cultures) and in vivo (mouse lung and lymphatic metastasis models) assays to evaluate the function of TBL1XR1. TBL1XR1’s downstream signaling was delineated by phospho-kinase array and knockdown of candidate mediators. Analysis of clinical data showed that TBL1XR1 overexpression was correlated with worse prognosis. Functional assays showed that TBL1XR1 promoted stemness, epithelial–mesenchymal transition (EMT), and lung and lymphatic metastasis in GC cells. TBL1XR1 activated ERK1/2-Sox2 signaling and was dependent on signaling via PI3K/AKT, in GC stem-like cells distinguished by CD44 expression. Moreover, inhibition of these signaling proteins reversed chemoresistance in in vitro and in vivo models. Taken together, our results indicate that TBL1XR1 promotes stemness and metastasis in GC, making it a potential prognostic indicator. The PI3K/AKT-TBL1XR1-ERK1/2-Sox2 axis may represent a target for the treatment of GC.

Background: Numerous studies have shown that the short-term efficacy of three-dimensional (3D) laparoscopic radical gastrectomy (LG) is comparable to that of two-dimensional (2D)-LG. Whether 3D-LG affects the recurrence patterns of gastric cancer (GC) patients has not been investigated. Methods: From January 2015 to April 2016, a total of 419 patients were recruited for a phase III clinical trial (NCT02327481), which compared the short-term outcomes between the 2D and 3D groups. The long-term efficacy including recurrence patterns was compared between the 2D and 3D groups in this retrospective study. Multivariate analyses were performed to determine whether 3D-LG affects the recurrence patterns. Results: Ultimately, 401 patients were analyzed (197 in the 2D-LG group and 204 in the 3D-LG group), and no differences were observed in the clinicopathological data between the two groups. There were no significant differences between the two groups in the recurrence types, first recurrence time or recurrence-free survival (RFS) (all p?>?0.05). According to the 7th American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system, both groups were stratified into pathological stages I, II, and III. The stratified analysis showed no significant differences in RFS or overall survival (OS) among patients in each subgroup (all p?>?0.05). The multivariate analysis of RFS showed that tumor diameter, pTNM stage, lymphovascular invasion, and adjuvant chemotherapy were independent factors (all p?<?0.05). The multivariate analysis of post-recurrence survival (PRS) showed that adjuvant chemotherapy was an independent protective factor (p?=?0.043). Conclusions: 3D-LG for GC did not differ significantly from 2D-LG in the effects on 3-year recurrence patterns, RFS and OS, which provides more tumor-related evidence for 3D technology. And due to the technological similarity, it may have certain reference value for robotic-assisted gastrectomy. Further multicenter, large-scale clinical trials are warranted.

Background: Previous retrospective studies have shown that laparoscopic spleen-preserving D2 total gastrectomy (LSTG) for advanced upper third gastric cancer (AUTGC) is safe. However, all previous studies were underpowered. We therefore conducted a prospective, multicenter study to evaluate the technical safety and feasibility of LSTG for patients with AUTGC. Methods: Patients diagnosed with AUTGC (cT2-4a, N−/+, M0) underwent LSTG at 19 institutions between September 2016 and October 2017 were included. The number of No. 10 lymph node (LN) dissections, metastasis rates, intraoperative and postoperative complications were investigated. Results: A total of 251 patients were enrolled in the study, and 242 patients were eligible for the per protocol analysis. The average numbers of No. 10 LN dissections and metastases were 2.4 and 0.1, respectively. Eighteen patients (7.4%) had No. 10 LN metastases, and among patients with advanced gastric cancer, the rate of No. 10 LN metastasis was 8.1% (18/223). pN3 status was an independent risk factor for No. 10 LN metastasis. Intraoperative complications occurred in 7 patients, but no patients required conversion to open surgery or splenectomy. The overall postoperative complication rate was 13.6% (33/242). The major complication and mortality rates were 3.3% (8/242) and 0.4% (1/242), respectively. The number of retrieved No. 10 LNs, No. 10 LN metastasis and TNM stage had no significant influence on postoperative complication rates. Conclusion: LSTG for AUTGC was safe and effective when performed by very experienced surgeons, this technique could be used in patients who needed splenic hilar lymph node dissection.

Background: Well-designed retrospective studies (RSs) and small-sample prospective studies (PSs) evaluating the efficacy of interventions have received much attention. This study was designed to evaluate the differences between well-designed RSs and small-sample randomized controlled trials based on the efficacy of laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) for advanced gastric cancer (GC). Methods: The clinicopathological data of 1360 patients with GC who underwent DG were analysed. After propensity score matching (1:1), 380 cases (ODG = 190, LDG = 190) were finally selected in a RS. Meanwhile, data from 120 patients (ODG = 60, LDG = 60) who enrolled in a PS were analysed. Results: In the PS, the LDG group had less intraoperative blood loss, shorter time to first flatus, and shorter time to fluid diet than the ODG group. In the RS, the LDG group had less intraoperative blood loss, and a shorter postoperative hospital stay than the ODG group. In the PS, the 3-year overall survival (OS) rate was 83.3% in the LDG group and 83.2% in the ODG group (p= 0.877). In the RS, the 3-year OS rate was 68.7% in the LDG group and 66.6% in the ODG group (p = 0.752). No significant interactions were observed between the two groups and any of the variables examined, either in the PS or RS. The recurrence patterns were similar in the two groups. Furthermore, Cox regression analysis showed that surgical method (LDG/ODG) was not a prognostic factor affecting OS or DFS, either prospectively or retrospectively. Conclusions: The oncologic efficacy of laparoscopic and open distal gastrectomy for advanced GC is comparable. Well-designed RSs can be similar to small sample of PSs in assessing long-term oncologic outcomes of surgical interventions, but the short-term outcomes obtained should be treated with caution.

IMPORTANCE: The application of indocyanine green (ICG) imaging in laparoscopic radical gastrectomy is in the preliminary stages of clinical practice, and its safety and efficacy remain controversial. OBJECTIVE: To investigate the safety and efficacy of ICG near-infrared tracer-guided imaging during laparoscopic D2 lymphadenectomy in patients with gastric cancer. DESIGN, SETTING, AND PARTICIPANTS: Patients with potentially resectable gastric adenocarcinoma (clinical tumor stage cT1-cT4a, N0/+, M0) were enrolled in a prospective randomized clinical trial at a tertiary referral teaching hospital between November 2018 and July 2019. Patients were randomly assigned to the ICG group or the non-ICG group. The number of retrieved lymph nodes, rate of lymph node noncompliance, and postoperative recovery data were compared between the groups in a modified intention-to-treat analysis. Statistical analysis was performed from August to September 2019. INTERVENTIONS: The ICG group underwent laparoscopic gastrectomy using near-infrared imaging after receiving an endoscopic peritumoral injection of ICG to the submucosa 1 day before surgery. MAIN OUTCOMES AND MEASURES: Total number of retrieved lymph nodes. RESULTS: Of 266 participants randomized, 133 underwent ICG tracer-guided laparoscopic gastrectomy, and 133 underwent conventional laparoscopic gastrectomy. After postsurgical exclusions, 258 patients were included in the modified intention-to-treat analysis, which comprised 129 patients (86 men and 43 women; mean [SD] age, 57.8 [10.7] years) in the ICG group and 129 patients (87 men and 42 women; mean [SD] age, 60.1 [9.1] years) in the non-ICG group. The mean number of lymph nodes retrieved in the ICG group was significantly more than the mean number retrieved in the non-ICG group (mean [SD], 50.5 [15.9] lymph nodes vs 42.0 [10.3] lymph nodes, respectively; P < .001). Significantly more perigastric and extraperigastric lymph nodes were retrieved in the ICG group than in the non-ICG group. In addition, the mean total number of lymph nodes retrieved in the ICG group within the scope of D2 lymphadenectomy was also significantly greater than the mean number retrieved in the non-ICG group (mean [SD], 49.6 [15.0] lymph nodes vs 41.7 [10.2] lymph nodes, respectively; P < .001). The lymph node noncompliance rate of the ICG group (41 of 129 patients [31.8%]) was lower than that of the non-ICG group (74 of 129 patients [57.4%]; P < .001). The postoperative recovery process was comparable, and no significant difference was found between the ICG and non-ICG groups in the incidence (20 of 129 patients [15.5%] vs 21 of 129 [16.3%], respectively; P = .86) or severity of complications within 30 days after surgery. CONCLUSIONS AND RELEVANCE: Indocyanine green can noticeably improve the number of lymph node dissections and reduce lymph node noncompliance without increased complications in patients undergoing D2 lymphadenectomy. Indocyanine green fluorescence imaging can be performed for routine lymphatic mapping during laparoscopic gastrectomy, especially total gastrectomy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03050879

Background: To compare the differences in occurrence rates, time intervals, main causes, and management strategies of early unplanned reoperations (EUROs) after gastrectomy for gastric cancer (GC) between laparoscopic and open surgery. Methods: From Jan. 2005 to Dec. 2014, 2608 and 1516 patients underwent laparoscopic-assisted gastrectomy (LAG) and open gastrectomy (OG), respectively. Perioperative outcomes and risk factors for EURO were analyzed. Results: The overall EURO rate was 1.3%, and the rate in LAG and OG groups was 1.1% and 1.6%, respectively. The EURO rate after 24 h postoperatively was significantly lower in LAG group than in OG group (p?=?0.019). No significant correlation was identified between laparoscopic surgery and EURO rate (p?=?0.157); age?>?70 (p?=?0.028), body mass index (BMI)?>?25 kg/m2(p?=?0.009), and estimated blood loss?>?100 ml (p?=?0.029) were independent risk factors for EURO. The main cause of EURO was intra-abdominal bleeding, anastomotic bleeding, and anastomotic leakage in LAG group; and intra-abdominal bleeding, anastomotic leakage, and intestinal obstruction in OG group. The proportion of patients with intra-abdominal bleeding requiring EURO was markedly higher in LAG group than in OG group (p?=?0.043). Transverse mesocolonic vessels and spleen were the most common bleeding sites necessitating EURO in LAG and OG groups, respectively. Six of 28 (21.4%) patients with EUROs in LAG group underwent laparoscopic procedure (p?=?0.025). Mortality in patients requiring EURO was 3.6% and 20.8% in LAG and OG groups, respectively (p?=?0.084). Conclusions: Compared to open surgery, laparoscopic surgery does not increase the incidence of EURO in patients undergoing gastrectomy for GC; however, laparoscopic surgery is associated with a lower EURO rate after 24 h postoperatively and a higher proportion of patients with intra-abdominal bleeding requiring EURO than open surgery. Effective and accurate intraoperative hemostasis for intra-abdominal vessels and anastomotic sites will help further reduce the incidence of EURO following LAG within 24 h postoperatively.

Three-dimensional (3D) systems for laparoscopy provide surgeons with additional information on spatial depth not found in two-dimensional (2D) systems. This study enrolled 156 spleen-preserving splenic hilar lymphadenectomy (LSPSHL) patients in a randomized controlled trial (ClinicalTrials.gov Identifier NCT02327481) at the department of gastric surgery at Fujian Medical University Union Hospital between January 2015 and April 2016. The short-term efficacies were compared between the treatment groups. The unedited videos of 80 LSPSHL (40 procedures each for 3D and 2D) were rated for technical performance using the Generic Error Rating Tool. The data for 156 LSPSHL patients indicate that the estimated blood loss (EBL) (3D vs 2D = 66.3 vs. 99.0, P= 0.046) was significantly less in the 3D group. The postoperative recovery and complication rates were similar (P> 0.05). And there were no deaths within 30 days of surgery. Two observers analyzed 80 videos of LSPSHL. The results showed that there were fewer grasping-errors made in the 3D group than in the 2D group when dissecting the inferior pole region of spleen (IPRS) (P= 0.016) and the superior pole region of spleen (SPRS) (P= 0.022). Additionally, the inter-rater reliability was high regarding grasping-errors in the IPRS (intraclass correlation coefficient (ICC) 0.92) and in the SPRS (ICC 0.83). The ICC for the total number of errors was 0.82. The mean of errors in the 3D group (3D vs. 2D = 20.7 vs. 23.5, P= 0.022) was less than the 2D group. Compared with 2D LSPSHL, 3D technology reduces EBL and technical errors during splenic hilar dissection.

To provide individualized survival predictors for patients after radical gastrectomy and to guide adjuvant treatment.

To determine whether laparoscopic surgery can be used in high-risk patients with gastric cancer. The clinicopathological data of 3743 patients with primary gastric adenocarcinoma, collected from January 2007 to December 2014, were retrospectively analyzed. Patients who had ≥ 1 of the following conditions were defined as high-risk patients: (1) age ≥ 80 years; (2) BMI ≥ 30 kg/m2; (3) ASA (American Society of Anesthesiologists) grade ≥ 3; or (4) clinical T stage 4 (cT4). Propensity score matching (PSM) was used to reduce confounding bias; then, we compared the short-term and long-term efficacy of laparoscopic gastrectomy (LG) with open gastrectomy (OG) in high-risk patients with gastric cancer. A total of 1296 patients were included in PSM. After PSM, no significant difference in clinicopathological data was observed between the LG group (n= 341) and the OG group (n= 341). The operative time (181.70 vs. 266.71 min, p< 0.001) and blood loss during the operation (68.11 vs. 225.54 ml, p< 0.001) in the LG group were significantly lower than those in the OG group. In the LG and OG groups, postoperative complications occurred in 39 (11.4%) and 63 (18.5%) patients, respectively, p= 0.010. Multivariate analysis showed that laparoscopic surgery was an independent protective factor against postoperative complications (p= 0.019). The number of risk factors was an independent risk factor for postoperative complications (p= 0.021). The 5-year overall survival rate in the LG group was comparable to that in the OG group (55.0 vs. 52.0%, p= 0.086). Hierarchical analysis further confirmed that the LG and OG groups exhibited comparable survival rates among patients with stages cI, pI, cII, pII, cIII, and pIII (all p> 0.05). For high-risk patients with gastric cancer, LG not only exhibits better short-term efficacy than OG but also has a comparable 5-year survival rate to OG.

The proportion of elderly patients who undergo surgery has rapidly increased. However, clinical indicators that predict outcomes are limited. Frailty is thought to estimate physiological reserves, although its use has not been evaluated in laparoscopic surgical patients. This study aimed to evaluate the significance of preoperative modified frailty index (PMFI) in octogenarians undergoing a laparoscopic gastrectomy. We reviewed prospectively collected data from 119 patients with gastric cancer (GC) aged 80 years or older who underwent a radical laparoscopic gastrectomy (RLG) between January 2007 and December 2012. Three baseline frailty traits were measured using routine preoperative laboratory data: albumin < 3.4 g/dL, haematocrit < 35%, and creatinine > 2 mg/dL. Patients were categorized by the number of positive traits as follows: low preoperative modified frailty index (LPMFI): 0–2 traits and high preoperative modified frailty index (HPMFI): 3 traits. We compared patient characteristics, operative outcomes, pathological results, morbidity, and survival. A total of 43 (36.1%) patients were considered HPMFI, and 76 (63.9%) patients were considered LPMFI. HPMFI was associated with an increased risk of postoperative complications (HPMFI group: odds ratio 2.506; 95% CI, 1.113–5.643, P= 0.027). With a median follow-up of 39.0 months, the 3-year overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) rates for the entire cohort were 47.9, 34.3, and 51.7%, respectively. Significant differences were observed in OS (HPMFI group, 37.2%; LPMFI group, 53.9%; P= 0.038) and RFS (HPMFI group, 23.3%; LPMFI group, 40.5%; P= 0.012) between the groups, but no difference was found for CSS (HPMFI group, 43.5%; LPMFI group, 56.4%; P= 0.078). HPMFI based on an easily calculable preoperative measure may be useful for predicting postoperative complications and have a negative impact on 3-year OS and RFS after an RLG in octogenarians. Therefore, HPMFI can serve as a low-cost, simple screen for high-risk individuals who might suffer more than expected during the postoperative period after an RLG.

To investigate oncologic efficacy of prophylactic laparoscopic superior mesenteric vein (No. 14v) lymph node (LN) dissection for lower-third gastric cancer (LTGC). We retrospectively collected data from 757 patients who underwent laparoscopic-assisted distal gastrectomy for LTGC. Of these patients, 102 underwent 14v LN dissection (14vD+ group), and the remaining 655 patients did not undergo 14v LN dissection (14vD− group). The outcomes were compared using a 1:1 propensity score matching method. After matching, 93 patients from the 14vD+ group and 93 patients from the 14vD− group with similar clinicopathological characteristics were compared. Before matching, the overall survival (OS) was similar between the two groups (P= 0.742). After matching, the OS was greater in the 14vD+ group (P= 0.025). The status of 14v dissection was not a significant prognostic factor in the survival analyses, both before and after matching. However, a stratified analysis according to the independent factors in the OS showed that the OS in the 14vD+ group was higher than that in the 14vD− group for cT2-3 patients after matching. The forest plot of OS showed that after matching the 14vD+ group had a significantly higher 3-year OS rate than the 14vD− group in cT2-3 patients. The distribution of the therapeutic index demonstrated that the index of 14v LN was similar to those of Nos. 1, 7, 8a, 9, and 11p after matching. Adding laparoscopic 14v dissection for laparoscopic-assisted radical distal gastrectomy was safe and might improve the OS for clinically advanced LTGC without serosal invasion.

To evaluate the risk factors affecting unplanned reoperation (URO) after laparoscopic gastrectomy (LAG) for gastric cancer (GC) and establish a model to predict URO preoperatively. Between May 2007 and December 2014, we prospectively collected and retrospectively analyzed the data of 2608 GC patients who underwent LAG. Among them, 2580 patients not requiring an URO were defined as the Non-URO group, and 28 patients requiring an URO were defined as the URO group. Univariate, multivariate, and bootstrap analyses were performed to determine the independent predictors for URO, and a nomogram was constructed to preoperatively predict the rate of URO after LAG. Of the 2608 patients, the URO rate was 1.1% (28/2608) within the 30-day hospitalization. The mean URO time interval to first operation was 5.6 ± 5.5 (0.10–18.5) days. The main causes requiring URO were intraabdominal bleeding (57.1%), anastomotic bleeding (17.9%), anastomotic leakage (7.1%), and intraabdominal infection (7.1%). Compared to the Non-URO group, the URO group had a significantly longer hospital stay (p< 0.001) and significantly higher hospital fees (p< 0.001). The morbidity rate was 39.2% in the URO group and 14.5% in the non-URO group (p= 0.001), and mortality was 3.6% in the URO group and 0.2% in the non-URO group (p= 0.063). Multivariate analysis using bootstrap method revealed that age >70 years (odds ratio (OR) = 2.232, 95% confidence interval (CI) = 1.023–4.491, p= 0.028), male gender (OR = 32.983, 95% CI 1.405–25.343 × 106, p= 0.027), and body mass index (BMI) > 25 kg/m2(OR = 2.550, 95% CI 1.017–5.398, p= 0.012) were independent risk factors for URO. A multivariable nomogram model for predicting URO exhibited a strong optimism-adjusted discrimination (concordance index, 0.687). No significant correlation was noted between the URO rate and operative period by Spearman analysis (r= 0.012, p= 0.548). Age > 70 years, Male, and BMI > 25 kg/m2were independent risk factors for URO. Based on the three risk factors, we developed a simple and practical nomogram to predict URO preoperatively, which might aid surgeons in reducing the URO rate when planning to perform LAG for GC.

Few studies have evaluated the outcomes of laparoscopic-assisted total gastrectomy (LATG) for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). Thus, aim of this study was to investigate the surgical outcomes of LATG for Siewert type II and III AEG. Clinical data for 700 Siewert type II and III AEG patients were analyzed retrospectively. The short- and long-term outcomes were compared between the matched groups using a propensity score matching method. Before matching, the comorbidities, Siewert classifications and tumor invasion depths significantly differed between the LATG and open total gastrectomy (OTG) groups. After matching, the clinicopathologic characteristics were well balanced between the two groups. In addition, after matching, decreases in the operative time, amount of blood loss, time to resumption of a semifluid diet, and length of hospital stay and an increased number of lymph nodes (LNs) retrieved were observed in the LATG group compared with the OTG group. Further, a significantly higher 3-year overall survival rate (81.3 vs 66.4%; P= 0.011) and disease-free survival rate (77.5 vs 63.8%; P= 0.040) were observed for the Siewert type II AEG patients in the LATG group compared with those in the OTG group; however, the survival rates were similar for the Siewert type III AEG patients in the two groups (P= 0.853 and P= 0.844, respectively). LATG is associated with better short-term outcomes for Siewert type II and III AEG. In addition, it may result in an increased number of retrieved LNs and better long-term survival for Siewert type II AEG patients in particular.

In this study, we evaluated the short-term outcomes following three-dimensional (3D) or two-dimensional (2D) laparoscopic surgery for patients with gastric cancer. There is a lack of prospective evidence regarding the safety and efficacy of 3D versus 2D laparoscopic surgery for patients with gastric cancer. Therefore, we conducted a phase III single-center, prospective, randomized, controlled trial to compare 3D and 2D laparoscopic surgery for patients with gastric cancer. We compared operation time, intraoperative blood loss, number of lymph node dissections, morbidity, and mortality between the 3D and 2D groups following laparoscopic surgery for gastric cancer. The study is registered at ClinicalTrials.gov with ID number NCT02327481. A total of 228 patients were randomized (3D group 115 cases; 2D group 113 cases) between January 1, 2015 and September 1, 2015. Seven patients who underwent exploratory operations were excluded. Finally, a total of 221 patients were analyzed (3D group 109 cases, 2D group 112 cases). There were no significant differences between the two groups regarding the clinical pathological characteristics, operating time (3D vs. 2D, 184 ± 36 vs. 178 ± 37 min, P= 0.288), number of lymph node dissections (36 ± 14 vs. 37 ± 13, P= 0.698), time to first ambulation (2.27 ± 1.60 vs. 2.04 ± 0.84, P= 0.18), flatus (3.89 ± 1.49 vs. 3.69 ± 1.12, P= 0.255), liquid diet (4.88 ± 1.88 vs. 4.79 ± 1.57, P= 0.684), or duration of postoperative hospital stay (12.52 ± 4.83 vs. 12.63 ± 7.32, P= 0.903). The postoperative complication rates of the 3D and 2D groups were 18.3 and 16.1%, respectively, P= 0.723. No patients died during the postoperative hospital stay. However, the intraoperative blood loss in the 3D group was significantly lower than the 2D group (58 ± 75 vs. 78 ± 72 ml, P= 0.047). There was no significant difference in operation time and number of lymph node harvested between the 3D and 2D groups; however, 3D laparoscopic surgery may reduce the intraoperative blood loss compared to 2D procedure. Therefore, we conclude that this trial is safe and is thus ongoing.

Comorbidity is a predictor of postoperative complications in gastrectomy. However, it remains unclear which comorbidities are predictors of postoperative complications in gastric cancer patients who have undergone laparoscopy-assisted total gastrectomy (LATG). The purpose of this study was to evaluate the effect of comorbidities on the surgical outcomes of patients with gastric cancer after LATG. We retrospectively collected data on 1657 gastric cancer patients who underwent LATG between January 2008 and December 2015. We investigated the incidences, types, and risk factors for postoperative complications after LATG. Patients were enrolled in analysis to evaluate the effects of comorbidities on postoperative complications. The number of postoperative complications was associated with the number of comorbidities in the gastric cancer patients according to the operative period. Of the 1657 patients included in this study, 714 (43.1 %) had one or more comorbidities. Postoperative complications occurred in 283 patients (17.1 %), and 6 patients (0.4 %) died during hospitalization. With an increasing number of comorbidities, the incidence of local and systemic complications also increased. Univariate and multivariate analyses revealed that comorbidity was a predictive risk factor for local complications (OR 1.204, 1.014–1.431) and systemic complications (OR 1.237, 1.039–1.474). Diabetes mellitus, anemia, pulmonary disease, and renal dysfunction were found to be associated with postoperative complications, including abdominal bleeding, anastomotic leakage, and pneumonia. Our study has revealed that comorbidities could be a predictive risk factor for postoperative complications after LATG. Surgeons should carefully assess patients with full perioperative attention to some specific types of comorbidities.

To investigate the incidence of and factors associated with postoperative complications and failure to rescue following laparoscopic and open gastrectomy for gastric cancer. We analyzed the records of 4124 patients who underwent a laparoscopic or open gastrectomy for gastric cancer. One-to-one propensity score matching was performed to compare the difference between the two groups. A total of 4124 patients were included in the study, 627 of whom (15.2 %) developed postoperative complications. Postoperative deaths occurred in 23 (0.6 %) patients with serious complications. In the propensity score matching analysis with 1361 pairs, no significant differences in the rates of overall complications (14.2 vs. 16.5 %, p= 0.093) were observed between laparoscopic and open gastrectomy group. In-hospital mortality decreased in patients who underwent laparoscopic gastrectomy compared to patients who underwent open gastrectomy (0.3 vs. 1.2 %, p= 0.004). Failure to rescue rates were lower in patients who underwent laparoscopic gastrectomy (2.1 vs. 7.6 %, p= 0.008). Multivariate analysis showed that older age, tumor location, TNM stage classification, extent of gastric resection, operative time and intra-operative blood loss were adverse risk factors for postoperative complications. Laparoscopic gastrectomy was found to be a protective factor for failure to rescue. Complications associated with failure to rescue included abdominal bleeding, anastomotic leakage and cardiac events. In-hospital mortality increased as the number of complications per patient increased. Assuming equal competence with open and laparoscopic approaches of a surgeon, the proportion of patients with postoperative complications were similar among those who underwent laparoscopic gastrectomy compared to patients who underwent open gastrectomy. However, when complications occurred, patients with open gastrectomy were more likely to die.

The evidence regarding the long-term results of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPL) has only been rarely reported. The aim of this study was to investigate the feasibility and oncologic efficacy of LSPL for locally advanced proximal gastric cancer. From May 2007 to December 2012, we prospectively collected and retrospectively analyzed the data of 548 patients who underwent laparoscopic radical total gastrectomy due to proximal gastric cancer. The patients were grouped according to spleen-preserving splenic hilar lymphadenectomy (200 in the D2 group and 348 in the D2-group). The short- and long-term outcomes were compared between the two groups after propensity score matching. Before matching, TNM stages were significantly different between the D2 and D2-groups. After propensity score matching, the two groups were well balanced in clinicopathologic characteristics. After matching, the time for lymph node dissection was longer in the D2 group, but a greater number of lymph nodes were dissected; the estimated blood loss, time to first flatus and duration of hospital stay were similar in the two groups. Furthermore, no significant differences in morbidity and mortality were found. Before matching, the 3-year overall survival (OS) and disease-free survival (DFS) rates of the D2 group were comparable with those of the D2-group (62.4 vs. 57.7 %, p= 0.076). After matching, the 3-year OS remained comparable, but the D2 group showed significantly longer 3-year DFS (61.6 vs. 53.7 %, p= 0.034). Stratified analysis showed that, in stage III patients, the D2 group had better 3-year DFS. Multivariate Cox regression showed that age (p= 0.003), operation (p= 0.001) and pN stage (p< 0.001) were independent prognostic factors. LSPL is a safe and feasible procedure, and patients with stage III proximal gastric cancer might obtain higher 3-year DFS rates.

To evaluate the safety, feasibility and clinical results of the modified delta-shaped gastroduodenostomy (MDSG) in totally laparoscopic distal gastrectomy (TLDG) for gastric cancer (GC). We performed a case–control and case-matched study enrolling 642 patients with GC undergoing laparoscopic distal gastrectomy with Billroth-I anastomosis from January 2011 to December 2014. TLDG with MDSG was performed in 158 patients (Group TL), and laparoscopy-assisted distal gastrectomy with circular anastomosis was performed in 484 patients (Group LA). One-to-one propensity score matching (PSM) was performed to compare the clinicopathological characteristics between the two groups. Patients with smaller tumors or stage I cancer were more likely to receive TLDG (P< 0.05). In the propensity-matched analysis of 143 pairs, there were no differences in demographic and pathologic characteristics between groups (all P< 0.05). All patients successfully underwent laparoscopic radical distal gastrectomy. Before PSM, Group TL had more dissected lymph nodes (LNs), a longer time to first fluid diet and a longer postoperative length of stay than Group LA (all P< 0.05). After PSM, except for the fact that more dissected LNs were obtained in Group LA (P< 0.05), no difference was found in the intraoperative and postoperative outcomes between the groups (all P> 0.05). The postoperative complications were similar in both groups (all P> 0.05). Stratification analysis performed after PSM showed that in early GC, no difference was observed in intraoperative and postoperative outcomes between the groups (all P> 0.05). However, in locally advanced GC, Group TL had more dissected LNs and a higher rate of postoperative complications (both P< 0.05). Univariate analysis carried out in locally advanced cases after PSM showed that the body mass index (BMI), the method of digestive tract reconstruction and Charlson’s score were significant factors that affected postoperative morbidity (all P< 0.05). Multivariate analysis indicated that BMI was an independent risk factor for postoperative morbidity (P< 0.05). The MDSG in TLDG is safe and feasible for early GC; however, it should be chosen with caution in advanced GC, particularly in patients with a high BMI.

The purpose of this study was to evaluate the risk factors that influence the difficulty of performing laparoscopic spleen-preserving splenic hilar lymph node dissection (SHLND) for gastric cancer and to establish a simple and effective scoring system to predict the surgical difficulty preoperatively. Between January 2011 and December 2013, we prospectively collected and retrospectively analyzed the medical records of 317 patients with upper- or middle-third gastric cancer who underwent laparoscopic spleen-preserving SHLND. Univariate and multivariate analyses were performed to determine the independent predictors for surgical difficulty based on the operation time during spleen-preserving SHLND. A logistic regression model was used to identify determinant variables and construct a predictive difficulty scoring system. Multivariate analysis showed that gender, body mass index (BMI), number of splenic lobar arteries (SLAs), and type of SLA were independently predictive factors of operation time. According to these factors, we developed a predictive surgical difficulty scoring system and the difficulty levels are divided into 0, 1, 2, 3, and 4 points or more. Based on the relative risk, we stratified the surgical difficulty into the following three divisions: 0 low difficulty, 1–2 intermediate difficulty, and 3 points or more high difficulty. The patients with long operation time accounted for 19.6, 43.6, and 90.9 % for the three groups, respectively (p< 0.001). The area under the receiver operating characteristic curve for the logistic regression model and the simplified difficulty scoring prediction model was 0.717 and 0.715, respectively. Based on four independent risk factors, including gender, BMI, number of SLAs, and type of SLA, we developed a simple and effective scoring system to predict the difficulty of laparoscopic spleen-preserving SHLND preoperatively. This novel scoring system might aid surgeons with different experience in performing operations at different levels of difficulty.

A scoring system allows risk stratification of morbidity might be helpful for selecting risk-adapted interventions to improve surgical safety. Few studies have been designed to develop scoring systems to predict SSIs after laparoscopic gastrectomy for gastric cancer. We analyzed the records of 2364 patients who underwent laparoscopic gastrectomy for gastric cancer. A logistic regression model was used to identify the determinant variables and develop a predictive score. There were 2364 patients, of whom 131 (5.5 %) developed overall SSIs, 33 (1.4 %) developed incisional SSIs, and 98 (4.1 %) developed organ/space SSIs. No significant risk factor was associated with incisional SSIs. A multivariate analysis showed the following adverse risk factors for organ/space SSIs: BMI ≥ 25 kg/m2, intraoperative blood loss ≥75 ml, operation time ≥240 min, and perioperative transfusion. Each of these factors contributed 1 point to the risk score. The organ/space SSIs rates were 1.8, 3.9, 9.9, and 39.0 % for the low-, intermediate-, high-, and extremely high-risk categories, respectively (p< 0.001). The area under the receiver operating characteristic curve for the score of organ/space SSIs was 0.734. There were no statistically significant differences between the observed and predicted incidence rates for organ/space SSIs in the validation set. This validated and simple scoring system could accurately predict the risk of organ/space SSIs after laparoscopic gastrectomy for gastric cancer. The score might be helpful in the selection of risk-adapted interventions to decrease the incidence rates of organ/space SSIs.

To validate the efficacy and safety of laparoscopic total gastrectomy (LTG) for advanced gastric cancer (AGC). Laparoscopic distal gastrectomy (LDG) in the treatment of patients with local AGC is becoming increasingly popular, and there have been several multicenter randomized controlled trials focused on this treatment. However, few reports on the procedure of LTG for AGC exist. The data of 976 patients who underwent LTG for AGC were retrieved from a prospectively constructed database of 2170 patients who underwent laparoscopic gastrectomy between 2007 and 2013. Surgical outcomes of LTG were investigated and compared with those of patients who underwent LDG. LTG was associated with significantly longer operation time, number of dissected lymph nodes, and time of resume soft diet compared with the LDG group. According to Clavien–Dindo classification, the morbidity and mortality rates of the LTG group were comparable to those of the LDG group. Multivariate analyses revealed that elderly patients, more comorbidities, and longer operation time were the significant independent risk factors for determining postoperative complications. The difference in overall survival rates between the two groups was statistically significant. However, a comparative analysis of overall survival showed no statistical significance for any of the stages of cancer between the LTG and LDG groups. The study findings suggest that LTG is an oncologically safe procedure for AGC yields comparable surgical outcomes. A well-designed phase III trial can be carried out to provide valuable evidence for the oncologic safety of LTG for the treatment of AGC.

Laparoscopic spleen-preserving total gastrectomy (LSPTG) for gastric cancer is only performed at a few specialized institutions and carries the risk of major perioperative complications (MPCs) that may require reoperation and impair recovery. However, the predictors of such events remain largely unknown. Prospectively collected data from 325 consecutive patients undergoing LSPTG at a single institution from June 2011 to February 2014 were analyzed to determine the preoperative factors that correlated with MPCs. The rates of MPCs were assessed, and a score model was developed to identify preoperative variables associated with MPC. Of the 325 LSPTG cases, the following types of MPCs were observed in 15 (4.6 %) patients: intraoperative splenic hilar vascular injury (n= 1); intraoperative splenic parenchymal injury (n= 5); intraoperative splenic infarction (n= 1); intraabdominal abscess that required radiological intervention [not under general anesthesia (n= 2)]; intra-abdominal bleeding that required reoperation under general anesthesia (n= 2); anastomotic hemorrhage that required reoperation under general anesthesia (n= 2); and death (n= 2). Three independent variables were correlated with MPCs in the multivariate analysis: body mass index (BMI) ≥25 kg/m2(odds ratio [OR] 3.992, 95 % confidence interval [CI] 1.210–13.175), tumor located at the greater curvature (OR 3.922, 95 % CI 1.194–12.880), and No.10 LN metastases (OR 4.418, 95 % CI 1.250–13.770). A risk score consisting of one point for each preoperative risk factor (BMI ≥ 25 kg/m2or tumor location in the greater curvature), resulting in an overall score of 0–2 points for each patient, predicted an increased risk of MPCs. BMI, tumor location, and No.10 LN metastases were significantly associated with increased rates of MPCs. A simple, clinically relevant scoring system based on two preoperative variables was clinically useful in predicting MPC risk in patients undergoing LSPTG.

Laparoscopic surgery (LS) for remnant gastric cancer (RGC) is gaining interest [1–3]. However, due to adhesions to adjacent organs, displacement of anatomical structures, and changes in lymphatic flow triangulation, LS for RGC is considered challenging. In this study, we report our experience performing laparoscopic lymph node dissection for RGC following Billroth-II gastrectomy.

IMPORTANCE: Apatinib is a novel treatment option for chemotherapy-refractory advanced gastric cancer (GC), but it has not been evaluated in patients with locally advanced GC. OBJECTIVE: To investigate the effectiveness and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally advanced GC. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective, single-group, open-label, phase 2 nonrandomized controlled trial was conducted in 10 centers in southern China. Patients with M0 and either clinical T2 to T4 or N+ disease were enrolled between July 1, 2017, and June 30, 2019. Statistical analysis was performed from December 1, 2019, to January 31, 2020. INTERVENTIONS: Eligible patients received apatinib (500 mg orally once daily on days 1 to 21 and discontinued in the last cycle) plus SOX (S-1: 40-60 mg orally twice daily on days 1 to 14; oxaliplatin: 130 mg/m2 intravenously on day 1) every 3 weeks for 2 to 5 cycles. A D2 gastrectomy was performed 2 to 4 weeks after the last cycle. MAIN OUTCOMES AND MEASURES: The primary end point was R0 resection rate. Secondary end points were the response rate, toxic effects, and surgical outcome. RESULTS: A total of 48 patients (mean [SD] age, 63.2 [8.2] years; 37 men [77.1%]) were enrolled in this study. Forty patients underwent surgery (38 had gastrectomy, and 2 had exploratory laparotomy), with an R0 resection rate of 75.0% (95% CI, 60.4%-86.4%). The radiologic response rate was 75.0%, and T downstaging was observed in 16 of 44 patients (36.4%). The pathological response rate was 54.2% (95% CI, 39.2%-68.6%); moreover, this rate was significantly higher in patients who achieved a radiologic response compared with those who did not (12 [80.0%] vs 1 [20.0%]; P?=?.03) and in those who had an Eastern Cooperative Oncology Group Performance Status score of 0 (20 [76.9%] vs 10 [45.5%]; P?=?.03) or had tumors located in the upper one-third of the stomach (16 [61.5%] vs 7 [31.8%]; P?=?.04). Patients who achieved a pathological response (vs those who did not) had significantly less blood loss (median [range]: 60 [10-200] mL vs 80 [20-300] mL; P?=?.04) and significantly more lymph nodes harvested (median [range]: 40 [24-67] vs 32 [19-51]; P?=?.04) during surgery. Postoperative complications were observed in 7 of 38 patients (18.4%). Grade 3 toxic effects occurred in 16 of 48 patients (33.3%), and no grade 4 toxic effects or preoperative deaths were observed. CONCLUSIONS AND RELEVANCE: This nonrandomized controlled trial found that apatinib combined with SOX was effective and had an acceptable safety profile as a neoadjuvant treatment for locally advanced GC. A large-scale randomized clinical trial may be needed to confirm the findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03192735

To investigate the incidence and prognosis of intra-abdominal infectious complications (IaICs) after laparoscopic-assisted gastrectomy (LAG) and open radical gastrectomy (OG) for gastric cancer.

Robotic systems recently have been introduced to overcome technical limitations of conventional laparoscopic gastrectomy, especially for complex procedures [1]. We developed a set of procedural operation steps for robotic spleen-preserving splenic hilar lymphadenectomy, which is difficult and recommended in D2 lymph node (LN) dissection during total gastrectomy [2–4].

Chemoresistance is the major cause of gastric adenocarcinoma (GA) treatment failure. The mechanisms underlying chemoresistance remain incompletely understood. Here, we sought to identify genes differentially expressed between chemoresistant and chemosensitive GA and to validate the function of the top hit.