Textbook oncological outcomes and prognosis after curative gastrectomy in advanced gastric cancer: A multicenter study.

BACKGROUND: The impact of achieving textbook oncological outcome (TOO) as a multimodal therapy quality indicator on the prognosis of advanced gastric cancer (AGC) remains inadequately assessed. METHODS: Patients with AGC who underwent curative gastrectomy between January 2010 and December 2017 at two East Asian medical centers were included. TOO was defined as achieving the textbook outcome (TO) and receiving neoadjuvant and/or adjuvant chemotherapy (NCT or ACT). Cox and logistic regression models were used to identify prognostic and non-TOO-associated risk factors. RESULTS: Among 3626 patients, 57.6% achieved TOO (TOO group), exhibiting significantly better 5-year overall survival (OS) and disease-free survival (DFS) than the non-TOO group (both p < 0.05). Multivariate Cox regression identified TOO as an independent prognostic factor for 5-year OS (HR, 0.67; 95% CI, 0.61-0.74; p < 0.001) and DFS (HR, 0.73; 95% CI, 0.66-0.81; p < 0.001). Multivariate logistic regression showed that open gastrectomy, lack of health insurance, age ≥65 years, ASA score ≥ Ⅲ, and tumor size ≥50 mm are independent risk factors for non-achievement of TOO (all p < 0.05). On a sensitivity analysis of TOO's prognostic value using varying definitions of chemotherapy parameters, a stricter definition of chemotherapy resulted in a decrease in the TOO achievement rate from 57.6 to 22.3%. However, the associated reductions in the risk of death and recurrence fluctuated within the ranges of 33-39% and 28-37%, respectively. CONCLUSIONS: TOO is a reliable and stable metric for favorable prognosis in AGC. Optimizing the surgical approach and improving health insurance status may enhance TOO achievement.

Assessment of Laparoscopic Indocyanine Green Tracer-Guided Lymphadenectomy After Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of indocyanine green (ICG)-guided lymph node (LN) dissection during laparoscopic radical gastrectomy after neoadjuvant chemotherapy (NAC) in patients with LAGC. SUMMARY BACKGROUND DATA: Studies on ICG imaging use in patients with LAGC on NAC are rare. METHODS: Patients with gastric adenocarcinoma (clinical T2-4NanyM0) who received NAC were randomly assigned to receive ICG-guided laparoscopic radical gastrectomy or laparoscopic radical gastrectomy alone. Here, we reported the secondary endpoints including the quality of lymphadenectomy (total retrieved LNs and LN noncompliance) and surgical outcomes. RESULTS: Overall, 240 patients were randomized. Of whom, 236 patients were included in the primary analysis (118 in the ICG group and 118 in the non-ICG group). In the ICG group, the mean number of LNs retrieved was significantly higher than in the non-ICG group within the D2 dissection (48.2 vs. 38.3, P <0.001). The ICG fluorescence guidance significantly decreased the LN non-compliance rates (33.9% vs. 55.1%, P =0.001). In 165 patients without baseline measurable LNs, ICG significantly increased the number of retrieved LNs and decreased the LN non-compliance rate (P <0.05). For 71 patients with baseline measurable LNs, the quality of lymphadenectomy significantly improved in those who had a complete response (P <0.05) but not in those who did not (P >0.05). Surgical outcomes were comparable between the groups (P >0.05). CONCLUSIONS: ICG can effectively improve the quality of lymphadenectomy in patients with LAGC who underwent laparoscopic radical gastrectomy after NAC.

Laparoscopic radical gastrectomy for gastric cancer: Long-term outcome in a teaching center.

BACKGROUND: Laparoscopic gastrectomy for gastric cancer (GC) are increasing, yet the evidence of the relationship between the learning curve and long-term outcomes is limited. AIMS: To analyze the relationship between the learning curve and survival in GC patients over a 10-year period. METHODS: This retrospective cohort study studied 3674 patients who underwent laparoscopic radical gastrectomy for gastric cancer. Cusum and Cox regression analysis were used to assess the association between the surgeon's experience and the 3 years overall survival (OS). RESULTS: The 3-year OS of all patients was 71.8 %. This increase of 3-year OS was associated with laparoscopic cases (r = 0.638, p = 0.047). Analysis of the CUSUM curve showed a significant change in the 3-year OS of 1400 cases. Further propensity score matching (PSM) of patients during and after the learning curve (<1400 and ≥ 1400 cases) showed a significant difference in the 3-year OS between the two groups (68.5 % vs. 72.3 %, p = 0.045). Cox regression analysis verified that in ≥1400 cases, prior laparoscopic surgery (p = 0.045), textbook outcome (TO) and the number of retrieved lymph nodes (LNs) were independent protective factors. The LN non-compliance rate was an independent risk factor. In contrast, the rate of TO and the median number of retrieved LNs were significantly higher after the learning curve (≥1400 cases). Furthermore, the rates of LN non-compliance were significantly lower (p < 0.05). CONCLUSIONS: Increasing laparoscopic surgical experience is associated with surgical quality and prognostic improvement in patients with gastric cancer. But improvements in outcomes accrued slowly over a long period.

OSATS scoring confirms ICG enhancement of performance in laparoscopic radical gastrectomy: a post-hoc analysis of a randomized controlled trial.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging is effective in increasing the number of lymph node dissections during laparoscopic radical gastrectomy; however, no studies have attempted to explain this phenomenon. METHODS: This study utilized the data from a previous randomized controlled trial (FUGES-012 study) investigating ICG-guided laparoscopic radical gastrectomy performed between November 2018 and July 2019. The Objective Structured Assessments of Technical Skills (OSATS) scoring system was used to grade videos from the ICG and non-ICG groups. Patients with an OSATS score greater than 29 were classified as the high-OSATS population, while those with an OSATS score less than or equal to 29 were classified as the low-OSATS population. RESULTS: A total of 258 patients were included in the modified intention-to-treat analysis: 129 in the ICG group and 129 in the non-ICG group. The OSATS score of the ICG group was higher than that of the non-ICG group (29.6±2.6 vs. 26.6±3.6; P <0.001). The ICG group underwent a significantly higher mean total number of lymph node dissections than the non-ICG group (50.5±15.9 vs. 42.0±10.3; adjusted P <0.001). The group assigned to ICG use, better OSATS (high-OSATS) scores were observed, which correlated with greater D2 lymph node retrieval (54.1±15.0 vs. 47.2±8.7; adjusted P =0.039). Finally, the ICG group had a lower rate of lymph node noncompliance than that of the non-ICG group (31.8 vs. 57.4%; P <0.001). CONCLUSIONS: By applying the ICG fluorescence navigation technique, better OSATS scores were observed, which correlated with greater lymph node retrieval and a lower lymph node noncompliance rate, as recommended for individualized laparoscopic radical gastrectomy.

Neurotransmitter Receptor HTR2B Regulates Lipid Metabolism to Inhibit Ferroptosis in Gastric Cancer.

Nerves can support tumor development by secreting neurotransmitters that promote cancer cell proliferation and invasion. 5-Hydroxytryptamine (5-HT) is a critical neurotransmitter in the gastrointestinal nervous system, and 5-HT signaling has been shown to play a role in tumorigenesis. Here, we found that expression of the 5-HT receptor HTR2B was significantly elevated in human gastric adenocarcinoma tissues compared with nontumor tissues, and high HTR2B expression corresponded to shorter patient survival. Both 5-HT and a specific HTR2B agonist enhanced gastric adenocarcinoma cell viability under metabolic stress, reduced cellular and lipid reactive oxygen species, and suppressed ferroptosis; conversely, HTR2B loss or inhibition with a selective HTR2B antagonist yielded the inverse tumor suppressive effects. In a patient-derived xenograft tumor model, HTR2B-positive tumors displayed accelerated growth, which was inhibited by HTR2B antagonists. Single-cell analysis of human gastric adenocarcinoma tissues revealed enrichment of PI3K/Akt/mTOR and fatty acid metabolism-related gene clusters in cells expressing HTR2B compared with HTR2B-negative cells. Mechanistically, HTR2B cooperated with Fyn to directly regulate p85 activity and trigger the PI3K/Akt/mTOR signaling pathway, which led to increased expression of HIF1α and ABCD1 along with decreased levels of lipid peroxidation and ferroptosis. Together, these findings demonstrate that HTR2B activity modulates PI3K/Akt/mTOR signaling to stimulate gastric cancer cell survival and indicate that HTR2B expression could be a potential prognostic biomarker in patients with gastric cancer. SIGNIFICANCE: Nerve cancer cross-talk mediated by HTR2B inhibits lipid peroxidation and ferroptosis in gastric cancer cells and promotes viability under metabolic stress, resulting in increased tumor growth and decreased patient survival.

CDK5 promotes apoptosis and attenuates chemoresistance in gastric cancer via E2F1 signaling.

BACKGROUND: Chemoresistance is a major clinical challenge that leads to tumor metastasis and poor clinical outcome. The mechanisms underlying gastric cancer resistance to chemotherapy are still unclear. METHODS: We conducted bioinformatics analyses of publicly available patient datasets to establish an apoptotic phenotype and determine the key pathways and clinical significance. In vitro cell models, in vivo mouse models, and numerous molecular assays, including western blotting, qRT-PCR, immunohistochemical staining, and coimmunoprecipitation assays were used to clarify the role of factors related to apoptosis in gastric cancer in this study. Differences between datasets were analyzed using the Student's t-test and two-way ANOVA; survival rates were estimated based on Kaplan-Meier analysis; and univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors. RESULTS: Bulk transcriptomic analysis of gastric cancer samples established an apoptotic phenotype. Proapoptotic tumors were enriched for DNA repair and immune inflammatory signaling and associated with improved prognosis and chemotherapeutic benefits. Functionally, cyclin-dependent kinase 5 (CDK5) promoted apoptosis of gastric cancer cells and sensitized cells and mice to oxaliplatin. Mechanistically, we demonstrate that CDK5 stabilizes DP1 through direct binding to DP1 and subsequent activation of E2F1 signaling. Clinicopathological analysis indicated that CDK5 depletion correlated with poor prognosis and chemoresistance in human gastric tumors. CONCLUSION: Our findings reveal that CDK5 promotes cell apoptosis by stabilizing DP1 and activating E2F1 signaling, suggesting its potential role in the prognosis and therapeutic decisions for patients with gastric cancer.

Indocyanine green fluorescence imaging-guided versus conventional laparoscopic lymphadenectomy for gastric cancer: long-term outcomes of a phase 3 randomised clinical trial.

Indocyanine green (ICG) fluorescence imaging-guided lymphadenectomy has been demonstrated to be effective in increasing the number of lymph nodes (LNs) retrieved in laparoscopic gastrectomy for gastric cancer (GC). Previously, we reported the primary outcomes and short-term secondary outcomes of a phase 3, open-label, randomized clinical trial (NCT03050879) investigating the use of ICG for image-guided lymphadenectomy in patients with potentially resectable GC. Patients were randomly (1:1 ratio) assigned to either the ICG or non-ICG group. The primary outcome was the number of LNs retrieved and has been reported. Here, we report the primary outcome and long-term secondary outcomes including three-year overall survival (OS), three-year disease-free survival (DFS), and recurrence patterns. The per-protocol analysis set population is used for all analyses (258 patients, ICG [n = 129] vs. non-ICG group [n = 129]). The mean total LNs retrieved in the ICG group significantly exceeds that in the non-ICG group (50.5 ± 15.9 vs 42.0 ± 10.3, P < 0.001). Both OS and DFS in the ICG group are significantly better than that in the non-ICG group (log-rank P = 0.015; log-rank P = 0.012, respectively). There is a difference in the overall recurrence rates between the ICG and non-ICG groups (17.8% vs 31.0%). Compared with conventional lymphadenectomy, ICG guided laparoscopic lymphadenectomy is safe and effective in prolonging survival among patients with resectable GC.

A scoring model for predicting early recurrence of gastric cancer with normal preoperative tumor markers: A multicenter study.

INTRODUCTION: Prognostic factors for postoperative early recurrence (ER) of gastric cancer (GC) in patients with normal or abnormal preoperative tumor markers (pre-TMs) remain unclear. MATERIALS AND METHODS: 2875 consecutive patients with GC who underwent radical gastrectomy (RG) between January 2010 and December 2016 were enrolled and randomly divided into training and internal validation groups. ER was defined as recurrence within two years of gastrectomy. Normal pre-TMs were defined as CEA≤5 ng/mL and CA199 ≤ 37 U/mL. Least absolute shrinkage selection operator (LASSO) Cox regression analysis was used to screen ER predictors. The scoring model was validated using 546 patients from another hospital. RESULTS: A total of 3421 patients were included. Multivariate Cox analysis showed that pre-TMs was an independent prognostic factor for ER. Survival after ER was equally poor in the normal and abnormal pre-TMs groups (P = 0.160). Based on LASSO Cox regression, the ER of patients with abnormal pre-TMs was only associated with the pT and pN stages; however, in patients with normal pre-TMs, it was also associated with tumor size, perineural invasion, and prognostic nutritional index. Scoring model constructed for patients with normal pre-TMs had better predictive performance than TNM staging (concordance-index:0.826 vs. 0.807, P < 0.001) and good reproducibility in both validation sets. Moreover, through risk stratification, the scoring model could not only identify the risk of ER but also distinguish ER patterns and adjuvant chemotherapy benefit subgroups. CONCLUSION: pre-TMs is an independent prognostic factor for ER in GC after RG. The established scoring model demonstrates excellent predictive performance and clinical utility.

Loss of ATOH1 in Pit Cell Drives Stemness and Progression of Gastric Adenocarcinoma by Activating AKT/mTOR Signaling through GAS1.

Gastric cancer stem cells (GCSCs) are self-renewing tumor cells that govern chemoresistance in gastric adenocarcinoma (GAC), whereas their regulatory mechanisms remain elusive. Here, the study aims to elucidate the role of ATOH1 in the maintenance of GCSCs. The preclinical model and GAC sample analysis indicate that ATOH1 deficiency is correlated with poor GAC prognosis and chemoresistance. ScRNA-seq reveals that ATOH1 is downregulated in the pit cells of GAC compared with those in paracarcinoma samples. Lineage tracing reveals that Atoh1 deletion strongly confers pit cell stemness. ATOH1 depletion significantly accelerates cancer stemness and chemoresistance in Tff1-CreERT2; Rosa26Tdtomato and Tff1-CreERT2; Apcfl/fl ; p53fl/fl (TcPP) mouse models and organoids. ATOH1 deficiency downregulates growth arrest-specific protein 1 (GAS1) by suppressing GAS1 promoter transcription. GAS1 forms a complex with RET, which inhibits Tyr1062 phosphorylation, and consequently activates the RET/AKT/mTOR signaling pathway by ATOH1 deficiency. Combining chemotherapy with drugs targeting AKT/mTOR signaling can overcome ATOH1 deficiency-induced chemoresistance. Moreover, it is confirmed that abnormal DNA hypermethylation induces ATOH1 deficiency. Taken together, the results demonstrate that ATOH1 loss promotes cancer stemness through the ATOH1/GAS1/RET/AKT/mTOR signaling pathway in GAC, thus providing a potential therapeutic strategy for AKT/mTOR inhibitors in GAC patients with ATOH1 deficiency.

A Novel ypTLM Staging System Based on LODDS for Gastric Cancer After Neoadjuvant Therapy: Multicenter and Large-Sample Retrospective Study.

BACKGROUND: The accuracy of the eighth AJCC ypTNM staging system on the prognosis of gastric cancer (GC) patients after neoadjuvant therapy (NAT) is controversial. This study aimed to develop and validate a novel staging system using the log odds of positive lymph nodes scheme (LODDS). METHODS: A retrospective analysis of 606 GC patients who underwent radical gastrectomy after neoadjuvant therapy was conducted as the development cohort. (Fujian Medical University Affiliated Union Hospital (n = 183), Qinghai University Affiliated Hospital (n = 169), Mayo Clinic (n = 236), Lanzhou University First Hospital (n = 18)). The validation cohort came from the SEER database (n = 1701). A novel ypTLoddsS (ypTLM) staging system was established using the 3-year overall survival. The predictive performance of two systems was compared. RESULTS: Two-step multivariate Cox regression analysis in both cohorts showed that ypTLM was an independent predictor of overall survival of GC patients after neoadjuvant therapy (HR: 1.57, 95% CI: 1.30-1.88, p < 0.001). In the development cohort, ypTLM had better discrimination ability than ypTNM (C-index: 0.663 vs 0.633, p < 0.001), better prediction homogeneity (LR: 97.7 vs. 70.9), and better prediction accuracy (BIC: 3067.01 vs 3093.82; NRI: 0.36). In the validation cohort, ypTLM had a better prognostic predictive ability (C-index: 0.614 vs 0.588, p < 0.001; LR: 11,909.05 vs. 11,975.75; BIC: 13,263.71 vs 13,328.24; NRI: 0.22). The time-dependent ROC curve shows that the predictive performance of ypTLM is better than ypTNM, and the analysis of the decision curve shows that ypTLM achieved better net benefits. CONCLUSION: A LODDS-based ypTLM staging system based on multicenter data was established and validated. The predictive performance was superior to the eighth AJCC ypTNM staging system.

CDK5RAP3 acts as a tumour suppressor in gastric cancer through the infiltration and polarization of tumour-associated macrophages.

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.

Assessment of Laparoscopic Spleen-Preserving Hilar Lymphadenectomy for Advanced Proximal Gastric Cancer Without Invasion Into the Greater Curvature: A Randomized Clinical Trial.

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.

A national advanced training program for laparoscopic radical gastrectomy has a positive impact on surgical trainees: A before and after study (ATP-LRG-1).

BACKGROUND: Due to the high technical requirements of laparoscopic radical gastrectomy (LRG), establishing an effective training system to promote clinical technology and operation specifications is necessary. We aimed to evaluate the effect of a national advanced training program for LRG (ATP-LRG). MATERIALS AND METHODS: The contents of the training include the following: 1) detailed technique descriptions; 2) prevention and solving of intraoperative complications; 3) live surgery performance; 4) theory and practice of clinical research; 5) comments on trainees' videos; and 6) questions, answers, and discussions. This retrospective before and after study surveyed 875 trainees from January 2015 to October 2020. Endpoints were general surgical skills (GSS), laparoscopic gastrectomy acceptance (LGA), and clinical research possibilities (CRP). The analysis took place in December 2021. RESULTS: The response rate was 70.5% (617/875). ATP-LRG reportedly had a positive impact on the LRG practice of 99.5% (614/617) of trainees. Their GSS (before vs. after: 16.5 ± 3.7 vs. 20.3 ± 3.1, P < 0.001), LGA (4.2 ± 0.9 vs. 4.6 ± 0.7, P < 0.001), and CRP (2.6 ± 1.2 vs. 3.2 ± 1.1, P < 0.001) significantly improved. The improvement in GSS for those with professional titles of associate chief surgeons and below was significantly higher than that for chief surgeons (4.0 ± 3.0 vs 3.3 ± 2.4, P = 0.017), while those of LGA and CRP were not. The annual number of operations before training was negatively correlated with improvement in GSS (P < 0.001, Pearson's correlation coefficient: 0.14). Multivariate logistic regression showed that those with professional titles of associate chief surgeons and below (odds ratio [OR]: 1.719, 95% confidence interval [CI]: 1.038-2.846, P = 0.035), and with annual number of operations before training being <60, (OR: 5.257, 95% CI: 2.573-10.742, P < 0.001) were most prone to high-GSS improvement. CONCLUSION: The nationwide ATP-LRG facilitates the improvement of trainees' GSS, LGA, and CRP levels. Surgeons with lower professional titles and fewer performed operations are most likely to improve their GSS through training.

Textbook outcome, chemotherapy compliance, and prognosis after radical gastrectomy for gastric cancer: A large sample analysis.

BACKGROUND: This study aims to analyze the effect of textbook outcome (TO) on the long-term prognosis and adjuvant chemotherapy (AC) compliance of patients with gastric cancer (GC) in a single institute. MATERIALS AND METHODS: Consecutive patients who underwent radical gastrectomy with pathological stage I-III at Union Hospital of Fujian Medical University from January 2010 to June 2017 were included. TO was defined as receiving a complete-potentially curative status, ≥15 lymph nodes examined, hospital stay ≤21 days, and freedom from intraoperative and postoperative complications, re-intervention in 30 days, 30-day readmission to the hospital or intensive care unit, and 30-day postoperative mortality. RESULTS: Totally 3993 patients were included, of which 3361 (84.2%) patients achieved TO. The overall, disease-specific, and recurrence-free survival of patients achieving TO were significantly better than those of patients without achieving TO (all P < 0.05). The total number of AC cycles was greater and the interval from surgery to first AC was shorter in the TO group compared with the Non-TO group. Age >65 years old, open surgery, pT3-4 stage, and total radical gastrectomy (TG) were identified as related high-risk factors for failure to achieve TO. Laparoscopic surgery facilitated TO achievement in high-risk groups. CONCLUSION: TO is a reliable indicator of favorable prognosis of patients with GC and contributes to postoperative chemotherapy compliance. Age ≤65 years old, non-TG, pT1-2 stage, and laparoscopic surgery may promote the achievement of TO.

Development and validation of metabolic scoring to individually predict prognosis and monitor recurrence early in gastric cancer: A large-sample analysis.

PURPOSE: To develop and validate a simple metabolic score (Metabolic score, MS) for use in evaluating the prognosis of gastric cancer (GC) patients and dynamically monitor for early recurrence. METHODS: We retrospectively collected general clinicopathological data of patients who underwent radical gastrectomy for GC between September 2012 and December 2017 in the Department of Gastric Surgery of the Fujian Medical University Union Hospital. Using a random forest algorithm to screen preoperative blood indicators into the Least absolute shrinkage and selection operator (LASSO) model, we developed a novel MS to predict prognosis. RESULTS: Data of 1974 patients were used to develop and validate the model. Total cholesterol (TCHO), bilirubin (TBIL), direct bilirubin (DBIL), and 15 other metabolic indicators had significant predictive value for the prognosis using the random forest algorithm. In the overall population, 533 patients (27.0%) had high and 1441 (73%) had low MS status. High MS status was related to tumor progression. The KM curves of 3-year OS and RFS for training set patients showed low MS had a better prognosis than high MS (OS: 79.4% vs 59.7%, P < 0.001; RFS: 76.0% vs 56.2%, P < 0.001). CONCLUSIONS: We have developed and validated MS to predict the long-term survival of GC patients and allow early monitoring of recurrence. This will provide physicians with simple, economical, and dynamic tumor monitoring information.

Robotic spleen-preserving total gastrectomy shows better short-term advantages: a comparative study with laparoscopic surgery.

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.

Comparison of long-term outcomes after robotic versus laparoscopic radical gastrectomy: a propensity score-matching study.

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.

Association of Adjuvant Chemotherapy With Overall Survival Among Patients With Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy.

Importance: Neoadjuvant chemotherapy (NAC) is a standard treatment option for locally advanced gastric cancer (LAGC); however, the indications for adjuvant chemotherapy (AC) in patients with LAGC who received NAC remain controversial. Objective: To compare survival rates between patients with LAGC who received AC and those who did not after NAC followed by surgery. Design, Setting, and Participants: This multicenter, international cohort study included 353 patients with LAGC undergoing curative-intent gastrectomy after NAC at 2 tertiary referral teaching hospitals in China between June 1, 2008, and December 31, 2017. To externally validate the findings in the Chinese patients, 109 patients from the US and Italy between June 1, 2006, and June 30, 2013, were reviewed. The follow-up period of the Chinese patients was completed in December 2020, and the follow-up period of the Western patients was completed between February and July 2017. Data analysis was performed from December 1, 2020, to February 28, 2021. Exposures: Patients who received AC and those who did not were propensity score matched to evaluate the association of AC with survival. Main Outcomes and Measures: Overall survival (OS), disease-free survival, and disease-specific survival. Results: Of 353 patients from China (275 [78.1%] male; mean [SD] age, 58.0 [10.7] years), 262 (74.1%) received AC and 91 (25.9%) did not. After propensity score matching, the 3-year OS was significantly higher in patients who received AC (60.1%; 95% CI, 53.1%-68.1%) than in those who did not (49.3%; 95% CI, 39.8%-61.0%) (P = .02). Lymph node ratio (LNR) was significantly associated with AC benefit (P < .001 for interaction), and a plot of the interaction between LNR and AC demonstrated that AC was associated with improved OS in patients with higher (≥9%) LNRs (3-year OS: 46.6% vs 21.7%; P < .001), but not in patients with LNRs less than 9% (3-year OS: 73.9% vs 71.3%; P = .30). When stratified by AC cycles, only those patients who completed at least 4 AC cycles exhibited a significant survival benefit in the 6-month (hazard ratio, 0.56; 95% CI, 0.33-0.96; P = .03) and 9-month landmark analysis (hazard ratio, 0.50; 95% CI, 0.27-0.94; P = .03). In the external cohort, improved OS with AC administration was also found in patients with LNRs of 9% or greater (3-year OS: 53.0% vs 26.3%; P = .04). Conclusions and Relevance: In this cohort study, the administration of AC after NAC and resection of LAGC was associated with improved prognosis in patients with LNRs of 9% or greater. These findings suggest that LNR might be valuable in AC selection in future decision-making processes.

Postoperative follow-up for gastric cancer needs to be individualized according to age, tumour recurrence pattern, and recurrence time.

BACKGROUND: Few studies have reported the association between the pattern and time point of recurrence in different groups stratified by age in postoperative survival of patients with gastric cancer. METHODS: The clinicopathological data and recurrence data of 2028 patients with GC who underwent curative surgery from January 2010 to March 2015 were enrolled in this study. Patients were grouped according to age: young group (YG) (≤45 years old) (n = 180) and non-young group (OG) (>45 years old) (n = 1848). RESULTS: A total of 2028 patients were enrolled. The young group had better 5-year OS and DFS than the non-young group. In peritoneal recurrence, the cumulative incidence of recurrence in YG was higher than that in OG (P < 0.001). In distant recurrence, the cumulative incidence of recurrence YG was always lower than that of OG (P = 0.004). Recurrence hazard function varied over time between the two groups:in the peritoneal metastasis, the recurrence hazard for YG was higher and earlier than that of OG and the YG was observed during five years after surgery with two recurrence peaks in 8.5 months and in 41.5 months. In distant recurrence, the recurrence hazard for OG had an earlier and higher single peak than that of YG (6.0 months). CONCLUSION: The recurrence characteristics of patients with gastric cancer after curative resection between young group and older group are different. Personalized follow-up strategies should be developed according to the age and time point after operation for the early detection of recurrence and making decision for further treatment.