Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Comparison of totally robotic and totally laparoscopic gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: With the improvements in laparoscopic or robotic surgical techniques and instruments, a growing number of surgeons have attempted to complete all digestive tract reconstruction intracorporeally; these procedures include totally robotic gastrectomy (TRG) and totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the safety and feasibility of the TRG and compare the short-term outcomes of the TRG and TLG in patients with gastric cancer. METHODS: Between January 2018 and June 2023, 346 consecutive patients who underwent TRG or TLG at a high-volume academic gastric cancer specialty center were included. 1:1 propensity score matching (PSM) was performed to reduce confounding bias. The surgical outcomes, postoperative morbidity, and surgical burden were compared in PSM cohort. RESULTS: After PSM, a well-balanced cohort of 194 patients (97 in each group) was included in the analysis. The total operation time of the TRG group was significantly longer than that of the TLG group (244.9 vs. 213.0 min, P < 0.001). There was no significant difference in the effective operation time between the 2 groups (217.8 vs. 207.2 min, P = 0.059). The digestive tract reconstruction time of the TRG group was significantly shorter than that of the TLG group (39.4 vs. 46.7 min, P < 0.001). The mean blood loss in the TRG group was less than that in the TLG group (101.1 vs. 126.8 mL, P = 0.014). The TRG group had more retrieved lymph nodes in the suprapancreatic area than that in the TLG group (16.6 vs 14.2, P = 0.002). The TRG group had a lower surgery task load index (38.9 vs. 43.1, P < 0.001) than the TLG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.4% vs. 16.5%, P = 0.691). CONCLUSION: This study demonstrated that TRG is a safe and feasible procedure, and is preferable to TLG in terms of invasion and ergonomics. The TRG may maximize the superiority of robotic surgical systems and embodies the theory of minimally invasive surgery.

Robotic Gastrectomy Versus Laparoscopic Gastrectomy for Gastric Cancer: A Multicenter Cohort Study of 5402 Patients in China.

OBJECTIVE: A large-scale multicenter retrospective cohort study was conducted to compare the short- and long-term outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. SUMMARY OF BACKGROUND DATA: RG is being increasingly used worldwide, but data from large-scale multicenter studies on the short- and long-term oncologic outcomes of RG versus LG are limited. The potential benefits of RG compared with LG for gastric cancer remain controversial. METHODS: Data from eligible patients who underwent RG or LG for gastric cancer of 11 experienced surgeons from 7 centers in China between March 2010 and October 2019 were collected. The RG group was matched 1:1 with the LG group by using propensity score matching. The primary outcome was postoperative complications. RESULTS: After propensity score matching, a well-balanced cohort of 3552 patients was included for further analysis. The occurrence of overall complications (12.6% vs 15.2%, P = 0.023) was lower in the RG group than in the LG group. RG was associated with less blood loss (126.8 vs 142.5 mL, P < 0.001) and more retrieved lymph nodes in total (32.5 vs 30.7, P < 0.001) and in suprapancreatic areas (13.3 vs 11.6, P < 0.001).The long-term oncological outcomes were comparable between the two groups. CONCLUSIONS: The results of this multicenter study demonstrate that RG is a safe and effective treatment for gastric cancer when performed by experienced surgeons, although longer operation time and higher costs are still concerns about RG. This study provides evidence suggesting that RG may represent an alternative surgical treatment to LG.

Comparison of the Postoperative Complications Between Robotic Total and Distal Gastrectomies for Gastric Cancer Using Clavien-Dindo Classification: A Propensity Score-matched Retrospective Cohort Study of 726 Patients.

BACKGROUND: This study was designed to compare the postoperative complications after Robotic total gastrectomy (RTG) and robotic distal gastrectomy (RDG) and to systematically evaluate the safety and feasibility of RTG for the treatment of gastric cancer (GC). METHODS: Patients with GC who underwent RTG or RDG for curative intent between March 2010 and August 2019 were analyzed. We used propensity score matching (PSM) to reduce selection bias. The morbidity and mortality within 30 days after surgery between the RTG and the RDG groups were compared. RESULTS: According to Clavien-Dindo (C-D) classification, the morbidity and mortality of the RTG group were comparable to those of the RDG group. Subgroup analyses showed no significant difference between the RTG and RDG groups in all stratified parameters (all P > .05). Multivariate analysis revealed that age ≥70 years (P = .002) and surgeons' experience ≤25 cases (P = .013) were independent risk factors for overall complication. Surgeons' experience ≤25 cases (P = .010) was identified as an independent risk factor for severe complication. CONCLUSION: RTG is a safe and feasible surgical procedure for the treatment of GC with acceptable morbidity and mortality. More complications were observed for RTG, indicating that RTG is more invasive than RDG.

Reappraise role of No. 10 lymphadenectomy for proximal gastric cancer in the era of minimal invasive surgery during total gastrectomy: a pooled analysis of 4 prospective trial.

BACKGROUND: For patients with locally advanced proximal gastric cancer (LAPGC), the individualized selection of patients with highly suspected splenic hilar (No. 10) lymph node (LN) metastasis to undergo splenic hilar lymphadenectomy, is a clinical dilemma. This study aimed to re-evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) and to identify the population who would benefit from it. METHODS: A total of 1068 patients (D2 group = 409; D2 + No. 10 group = 659) who underwent laparoscopic total gastrectomy from four prospective trials between January 2015 and July 2019 were analyzed. RESULTS: No significant difference in the incidence (16.9% vs. 16.4%; P = 0.837) of postoperative complications were found between the two groups. The metastasis rate of No. 10 LN among patients in the D2 + No. 10 group was 10.3% (68/659). Based on the decision tree, patients with LAPGC with tumor invading the greater curvature (Gre), patients with non-Gre-invading LAPGC with a tumor size > 5 cm and clinical positive locoregional LNs were defined as the high-priority No. 10 dissection group. The metastasis rate of No. 10 LNs in the high-priority group was 19.4% (41/211). In high-priority group, the 3-year overall survival of the D2 + No. 10 group was better than that of the D2 group (74.4% vs. 42.1%; P = 0.005), and the therapeutic index of No. 10 was higher than the indices of most suprapancreatic stations. CONCLUSIONS: LSPSHL for LAPGC is safe and feasible when performed by experienced surgeons. LSPSHL could be recommended for the high-priority group patients even without invasion of the Gre.

Incidence and risk factors of postoperative complications after robotic gastrectomy for gastric cancer: an analysis of 817 cases based on 10-year experience in a large-scale center.

BACKGROUND: In this study, we investigated the incidence and risk factors for postoperative complications after robotic gastrectomy (RG) in patients with gastric cancer. METHODS: A total of 817 patients who underwent RG for gastric cancer between March 2010 and August 2019 were analyzed retrospectively. Postoperative complications were categorized according to the Clavien-Dindo classification, and possible risk factors were evaluated. RESULTS: Among 817 patients who underwent RG, overall, severe, local and systemic complication rates were 13.8, 4.2, 7.0 and 6.9%, respectively. Multivariable analysis revealed that an age of 70 years or older (P < 0.001) and multiorgan resection (P = 0.031) were independent risk factors for the occurrence of overall complications. Multivariable analysis showed that an age of 70 years or older (P = 0.005) and surgeons' experience ≤ 25 cases (P = 0.004) were independent risk factors for severe complications. Regarding local complications, an age of 70 years or older (P < 0.001), multiorgan resection (P = 0.010) and surgeons' experience ≤ 25 cases (P = 0.005) were identified as independent risk factors. An age of 70 years or older (P < 0.001), a BMI of 25 or higher (P = 0.045) and the presence of comorbidity (P = 0.029) were identified as independent risk factors for systemic complications. CONCLUSIONS: The present study demonstrated that RG is a safe and feasible procedure for the treatment of gastric cancer, and it has an acceptable postoperative morbidity. Elderly patients and insufficient surgeon experience were two major risk factors for the occurrence of complications following RG. We suggest that surgeons choose patients in good condition during their RG learning phase to reduce learning-associated morbidity.

Long-term oncologic outcomes of robotic versus laparoscopic gastrectomy for locally advanced gastric cancer: a propensity score-matched analysis of 1170 patients.

BACKGROUND: The robotic surgical system has several technical advantages over laparoscopic instruments. The technical feasibility and safety of robotic gastrectomy (RG) for gastric cancer have been reported by increasing number of studies. However, the long-term survival and recurrence outcomes after RG for locally advanced gastric cancer (AGC) have seldom been reported. This study aimed to compare long-term oncologic outcomes for patients with locally AGC after RG or laparoscopic gastrectomy (LG). METHODS: This study comprised 1170 patients underwent RG or LG, respectively, for locally AGC between March 2010 and February 2017. The primary outcome was the 3-year disease-free survival (DFS). The secondary endpoint included 3-year overall survival (OS) and recurrence patterns. One-to-one propensity score matching (PSM) was performed to reduce confounding bias. The outcomes were compared in PSM cohort. RESULTS: After PSM, a well-balanced cohort of 816 patients (408 in each group) were included in the analysis. The 3-year DFS rate was 76.2% in the robotic group and 70.1% in the laparoscopic group (P = 0.076). The 3-year OS rates was 76.7% in the robotic group and 73.3% in the laparoscopic group (P = 0.246). In the subgroup analyses for potential confounding variables, neither 3-year DFS nor 3-year OS survival were significantly different between the two groups (all P > 0.05). The two groups showed similar recurrence patterns within 3 years after surgery (P > 0.05). CONCLUSION: For patients with locally AGC, RG can result in comparable long-term survival outcomes without an increase in recurrence rate.

Safety and feasibility of laparoscopic spleen-preserving No. 10 lymph node dissection for locally advanced upper third gastric cancer: a prospective, multicenter clinical trial.

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.

Is Preoperative Fibrinogen Associated with the Survival Prognosis of Gastric Cancer Patients? A Multi-centered, Propensity Score-Matched Retrospective Study.

BACKGROUND: The prognostic significance of preoperative plasma fibrinogen in patients with operable gastric cancer remains under debate. This study aimed to elucidate the prognostic value of fibrinogen in gastric cancer patients underwent gastrectomy. METHODS: A total of 4351 patients with gastric cancer collected from three comprehensive medical centers were retrospectively evaluated. Patients were categorized by minimum P value using X-tile, while the baseline confounders for fibrinogen was balanced through propensity score matching (PSM). The relationships between fibrinogen and other clinicopathologic features were evaluated, and nomogram was constructed to assess its prognostic improvement compared with TNM staging system. RESULTS: Fibrinogen was significantly correlated with macroscopic type, tumor differentiation, tumor size, and T and N stage. The factors, fibrinogen and T stage as well as N stage, were identified to be independent prognostic factors after PSM. Nomogram based on fibrinogen demonstrated a smaller Akaike information criterion (AIC) and a larger concordance index (C-index) than TNM staging system, illustrating that fibrinogen might be able to improve the prognostic accuracy. CONCLUSIONS: Preoperative plasma fibrinogen levels in gastric cancer patients were significantly correlated with tumor progression, which could be regarded as a reliable marker for survival prognostic prediction.

Superiority of Tumor Location-Modified Lauren Classification System for Gastric Cancer: A Multi-Institutional Validation Analysis.

BACKGROUND: The tumor location-modified Lauren classification (mLC) has been proposed recently, but its clinical significance remains under debate. This study aimed to elucidate the clinical relevance of mLC and evaluate its superiority to the Lauren classification (LC) for gastric cancer patients with gastrectomy. METHODS: This study retrospectively evaluated 2764 consecutive gastric cancer patients from three comprehensive medical institutions. The patients were categorized into training, inner-validation, and independent validation sets. The relationships between mLC and other clinicopathologic factors were analyzed, and independent prognostic factors were identified. Survival prognostic discriminatory ability and predictive accuracy were compared between mLC and LC using the concordance index (C-index) and Akaike's information criterion (AIC), and a nomogram based on mLC was constructed to compare its prognostic improvement with the tumor-node metastasis (TNM) staging system. RESULTS: A significant association between mLC and gender, age, histologic type, T stage, N stage, and M stage was found. The findings showed that mLC, not LC, is an independent prognostic factor, with a smaller AIC and a higher C-index than LC. The nomogram based on mLC showed a better predictive ability than TNM alone. CONCLUSIONS: Compared with LC, mLC, which could be considered a more reliable prognostic factor, may improve the prognostic discriminatory ability and predictive accuracy for gastric cancer patients with gastrectomy.

Tumour-activated neutrophils in gastric cancer foster immune suppression and disease progression through GM-CSF-PD-L1 pathway.

OBJECTIVE: Neutrophils are prominent components of solid tumours and exhibit distinct phenotypes in different tumour microenvironments. However, the nature, regulation, function and clinical relevance of neutrophils in human gastric cancer (GC) are presently unknown. DESIGN: Flow cytometry analyses were performed to examine levels and phenotype of neutrophils in samples from 105 patients with GC. Kaplan-Meier plots for overall survival were performed using the log-rank test. Neutrophils and T cells were isolated, stimulated and/or cultured for in vitro and in vivo regulation and function assays. RESULTS: Patients with GC showed a significantly higher neutrophil infiltration in tumours. These tumour-infiltrating neutrophils showed an activated CD54+ phenotype and expressed high level immunosuppressive molecule programmed death-ligand 1 (PD-L1). Neutrophils activated by tumours prolonged their lifespan and strongly expressed PD-L1 proteins with similar phenotype to their status in GC, and significant correlations were found between the levels of PD-L1 and CD54 on tumour-infiltrating neutrophils. Moreover, these PD-L1+ neutrophils in tumours were associated with disease progression and reduced GC patient survival. Tumour-derived GM-CSF activated neutrophils and induced neutrophil PD-L1 expression via Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signalling pathway. The activated PD-L1+ neutrophils effectively suppressed normal T-cell immunity in vitro and contributed to the growth and progression of human GC in vivo; the effect could be reversed by blocking PD-L1 on these neutrophils. CONCLUSIONS: Our results illuminate a novel mechanism of PD-L1 expression on tumour-activated neutrophils in GC, and also provide functional evidence for these novel GM-CSF-PD-L1 pathways to prevent, and to treat this immune tolerance feature of GC.

Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression.

Interleukin 6 (IL-6) was abundant in the tumor microenvironment and played potential roles in tumor progression. In our study, the expression of IL-6 in tumor tissues from 36 gastric cancer (GC) patients was significantly higher than in non-tumor tissues. Moreover, the number of CD163+CD206+ M2 macrophages that infiltrated in tumor tissues was significantly greater than those infiltrated in non-tumor tissues. The frequencies of M2 macrophages were positively correlated with the IL-6 expression in GC tumors. We also found that IL-6 could induce normal macrophages to differentiate into M2 macrophages with higher IL-10 and TGF-ß expression, and lower IL-12 expression, via activating STAT3 phosphorylation. Accordingly, knocking down STAT3 using small interfering RNA decreased the expression of M2 macrophages-related cytokines (IL-10 and TGF-ß). Furthermore, supernatants from IL-6-induced M2 macrophages promote GC cell proliferation and migration. Moreover, IL-6 production and CD163+CD206+ M2 macrophage infiltration in tumors were associated with disease progression and reduced GC patient survival. In conclusion, our data indicate that IL-6 induces M2 macrophage differentiation (IL-10highTGF-ßhighIL-12 p35low ) by activating STAT3 phosphorylation, and the IL-6-induced M2 macrophages exert a pro-tumor function by promoting GC cell proliferation and migration.

miR-203 suppression in gastric carcinoma promotes Slug-mediated cancer metastasis.

MicroRNAs (miRNAs) play critical roles in tumorigenesis and cancer metastasis. Recently, miR-203 was reported as a tumor suppressor microRNA silenced in different malignancies including hepatocellular carcinoma, prostate cancer, oral cancer, breast cancer, and hematopoietic malignancy, whereas its role in the carcinogenesis of gastric carcinoma (GC) has not been evaluated. Here, we analyzed the levels of miR-203 and Slug in the GC specimen and studied their correlation. We analyzed the binding of miR-203 to the 3'-UTR of Slug messenger RNA (mRNA) and its effects on Slug translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-203 levels in GC cells and studied their effects on the cell invasiveness in transwell cell migration assay. We found that in GC, miR-203 levels were significantly decreased and Slug levels were significantly increased. miR-203 and Slug inversely correlated in patients' specimen. Bioinformatic analysis predicted that miR-203 may target the 3'-UTR of Slug mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Overexpression of miR-203 inhibited Slug and cell invasiveness, while depletion of miR-203 increased Slug and cell invasiveness. These data suggest that miR-203 suppression in GC promotes Slug-mediated cancer metastasis.

Dose-response meta-analysis of poultry intake and colorectal cancer incidence and mortality.

PURPOSE: Poultry intake has been inconsistently associated with incidence or mortality of colorectal cancer (CRC) in epidemiologic studies. The purpose of this study was to assess their relationships by performing a dose-response meta-analysis. METHODS: We conducted a search of PubMed database between January 1966 and July 2013 for prospective studies that reported relative risks (RRs) with 95 % confidence interval (CIs) of CRC for at least three categories of poultry intake. Dose-response relationships were examined with the generalized least-squares trend estimation. Study-specific results were pooled with a random-effects model. Subgroup, sensitivity, and meta-regression analyses were also conducted to explore heterogeneity. RESULTS: Sixteen studies on poultry intake and CRC incidence, and four studies regarding poultry intake and CRC mortality were identified. These studies involved a total of 13,949 incident CRC cases and 983 CRC deaths. The RRs of CRC for higher compared with lower intake of poultry were reported in these studies, and the reported levels of poultry intake varied substantially. Results of the dose-response meta-analysis conferred a RR of 0.89 (95 % CI 0.81-0.97) for an increase in poultry intake of 50 g/day. The results were not sensitive to any individual studies and were similar for colon and rectal cancer. Poultry intake was not associated with CRC mortality (RR for 50 g/day = 0.97, 95 % CI 0.79-1.20). CONCLUSIONS: This meta-analysis indicates that poultry intake may be moderately associated with reduced incidence of CRC.

CD8(+) T cells that produce interleukin-17 regulate myeloid-derived suppressor cells and are associated with survival time of patients with gastric cancer.

BACKGROUND & AIMS: CD8(+) T cells that produce interleukin (IL)-17 (Tc17 cells) promote inflammation and have been identified in tumors. We investigated their role in the pathogenesis of gastric cancer. METHODS: We used flow cytometry analyses to determine levels and phenotype of Tc17 cells in blood and tumor samples from 103 patients with gastric cancer. We performed multivariate analysis to identify factors associated with overall survival using the Cox proportional hazards model. CD8(+) T cells and monocytes were isolated and cocultured in an assay for induction of Tc17 cells. Tumor cells and myeloid-derived suppressor cells (MDSCs) were isolated and used in assays of Tc17 cell function. RESULTS: Tc17 cells with distinct cytokine and functional profiles were found in gastric tumor samples from patients. The percentage of Tc17 cells increased with tumor progression and was associated with overall survival time. Tumor-activated monocytes secreted IL-6, IL-1ß, and IL-23, which promoted development of Tc17 cell populations. Supernatants from cultured Tc17 cells induced production of the chemokine CXCL12 by tumor cells; this promoted CXCR4-dependent migration of MDSCs and impaired functions of anti-tumor CD8(+) cytotoxic T cells via a cell contact-dependent mechanism. CONCLUSIONS: Percentages of Tc17 cells in gastric tumors are associated with survival times of patients. These cells promote chemotaxis of MDSCs, which might promote tumor progression.

Novel combined endoscopic and laparoscopic surgery for advanced T2 gastric cancer: Two case reports.

BACKGROUND: The standard treatment for advanced T2 gastric cancer (GC) is laparoscopic or surgical gastrectomy (either partial or total) and D2 lymphadenectomy. A novel combined endoscopic and laparoscopic surgery (NCELS) has recently been proposed as a better option for T2 GC. Here we describe two case studies demonstrating the efficacy and safety of NCELS. CASE SUMMARY: Two T2 GC cases were both resected by endoscopic submucosal dissection and full-thickness resection and laparoscopic lymph nodes dissection. This method has the advantage of being more precise and minimally invasive compared to current methods. The treatment of these 2 patients was safe and effective with no complications. These cases were followed up for nearly 4 years without recurrence or metastasis. CONCLUSION: This novel method provides a minimally invasive treatment option for T2 GC, and its potential indications, effectiveness and safety needs to be further evaluated in controlled studies.

Increased intratumoral IL-22-producing CD4(+) T cells and Th22 cells correlate with gastric cancer progression and predict poor patient survival.

IL-22-producing CD4(+) T cells (IL-22(+)CD4(+) T cells) and Th22 cells (IL-22(+)IL-17(-)IFN-γ(-)CD4(+) T cells) represent newly discovered T-cell subsets, but their nature, regulation, and clinical relevance in gastric cancer (GC) are presently unknown. In our study, the frequency of IL-22(+)CD4(+) T cells in tumor tissues from 76 GC patients was significantly higher than that in tumor-draining lymph nodes, non-tumor, and peritumoral tissues. Most intratumoral IL-22(+)CD4(+) T cells co-expressed IL-17 and IFN-γ and showed a memory phenotype. Locally enriched IL-22(+)CD4(+) T cells positively correlated with increased CD14(+) monocytes and IL-6 and IL-23 detection ex vivo, and in vitro IL-6 and IL-23 induced the polarization of IL-22(+)CD4(+) T cells in a dose-dependent manner and the polarized IL-22(+)CD4(+) T cells co-expressed of IL-17 and IFN-γ. Moreover, IL-22(+)CD4(+) T-cell subsets (IL-22(+)IL-17(+)CD4(+), IL-22(+)IL-17(-)CD4(+), IL-22(+)IFN-γ(+)CD4(+), IL-22(+)IFN-γ(-)CD4(+), and IL-22(+)IL-17(+)IFN-γ(+)CD4(+) T cells), and Th22 cells were also increased in tumors. Furthermore, higher intratumoral IL-22(+)CD4(+) T-cell percentage and Th22-cell percentage were found in patients with tumor-node-metastasis stage advanced and predicted reduced overall survival. In conclusion, our data indicate that IL-22(+)CD4(+) T cells and Th22 cells are likely important in establishing the tumor microenvironment for GC; increased intratumoral IL-22(+)CD4(+) T cells and Th22 cells are associated with tumor progression and predict poorer patient survival, suggesting that tumor-infiltrating IL-22(+)CD4(+) T cells and Th22 cells may be suitable therapeutic targets in patients with GC.

Increased tumor-infiltrating CD8(+)Foxp3(+) T lymphocytes are associated with tumor progression in human gastric cancer.

BACKGROUND: CD8(+)Foxp3(+) T lymphocytes have been detected in tumors. However, the distribution, phenotypic features, and regulation of these cells in gastric cancer remain unknown. METHODS: The levels of CD8(+)Foxp3(+) T lymphocytes in the peripheral blood, tumor-draining lymph nodes, non-tumor tissues, and tumor tissues of patients with gastric cancer were detected by flow cytometry. Foxp3 induction in CD8(+)Foxp3(-) T cells was investigated in vitro. The suppressive function of CD8(+)Foxp3(+) T lymphocytes was analyzed by their effect on CD4(+) T-cell proliferation and IFN-γ production. The percentages of CD8(+)Foxp3(+) T lymphocytes were evaluated for the association with tumor stage. RESULTS: The frequency of CD8(+)Foxp3(+) T lymphocytes in tumor tissues was significantly higher than that in non-tumor tissues, and similar results were also observed in tumor-draining lymph nodes compared with peripheral blood. Most intratumoral CD8(+)Foxp3(+) T lymphocytes were activated effector cells (CD45RA(-)CD27(-)). TGF-ß1 levels were positively correlated with the frequency of CD8(+)Foxp3(+) T lymphocytes in tumor tissues, and in vitro TGF-ß1 could induce the generation of CD8(+)Foxp3(+) T lymphocytes in a dose-dependent manner. Furthermore, intratumoral CD8(+)Foxp3(+) T lymphocytes suppressed the proliferation and IFN-γ production of CD4(+) T cells. Finally, intratumoral CD8(+)Foxp3(+) T lymphocytes were significantly increased with tumor progression in terms of tumor-node-metastasis (TNM) stage. CONCLUSIONS: Our data have shown that increased intratumoral CD8(+)Foxp3(+) T lymphocytes are associated with tumor stage and potentially influence CD4(+) T-cell functions, which may provide insights for developing novel immunotherapy protocols against gastric cancer.

Application of stereology to study the effects of pneumoperitoneum on peritoneum.

BACKGROUND: Scanning electron microscopy is unable to provide sufficient data to obtain definitive results for research into the morphologic effect of pneumoperitoneum on peritoneum. To overcome this difficulty, we adopted stereology to examine the effect of the type of gas insufflated, pressure, duration, and gas flow on morphologic alterations of peritoneum. METHODS: Fifty SD rats were divided into ten groups. One group served as control. Pneumoperitoneum was established at 5 mmHg and 1.0 l/min gas flow for 1, 2 or 3 h with CO2 (in groups C1h, C2h, and C3h, respectively) or with He (in groups H1h, H2h, and H3h, respectively). CO2 pneumoperitoneum was further established at 8 mmHg and 1.0 l/min gas flow for 1 h (group C8p), at 5 mmHg and 2.0 l/min gas flow for 1 h (group C2f), and at 5 mmHg and 3.0 l/min gas flow for 1 h (group C3f). After the procedures, five specimens were sampled from anterior peritoneum and measured by stereological and electron-microscopic techniques. RESULTS: Groups H1h and C1h, H2h and C2h, and H3h and C3h, respectively, were the same in terms of area fraction of basal lamina exposed and diameter of mesothelial cells (P>0.05). The magnitudes of peritoneal trauma in groups C2h, C3h, C8p, C2f, and C3f were significantly higher than that in group C1h (P<0.01), and the same result was observed in groups H2h and H3h against group H1h (P<0.01), and in group C3f against group C2f (P<0.01). Furthermore, the area fractions of basal lamina exposed in groups C3h and H3h were remarkably higher than those in groups C2h and H2h, respectively (P<0.01). The mechanism of basal lamina exposure comprises mesothelial cell desquamation and plasmatorrhexis. CONCLUSIONS: Peritoneal morphologic trauma during pneumoperitoneum can be attributed to the pressure, duration, and gas flow instead of the type of gas insufflated.

Short-Term Clinical Efficacy of Neoadjuvant Chemotherapy Combined With Laparoscopic Gastrectomy for Locally Advanced Siewert Type II and III Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Propensity Score-Matched Study.

BACKGROUND: Laparoscopic gastrectomy (LG) has been increasingly used for the treatment of locally advanced Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). However, whether LG can achieve the same short-term efficacy in the treatment of patients who receive neoadjuvant chemotherapy (NACT) remains controversial. Thus, the aim of this study was to investigate the clinical outcomes of NACT combined with LG for Siewert type II and III AEG. METHODS: This retrospective study identified patients with locally advanced Siewert type II and III AEG diagnosed between May 2011 and October 2020 using the clinical tumor-node-metastasis (cTNM) staging system. The short-term outcomes were compared between the matched groups using a 1:3 propensity score matching (PSM) method, which was performed to reduce bias in patient selection. RESULTS: After PSM, 164 patients were selected, including 41 in the NACT group and 123 in the LG group. The baseline characteristics were similar between the two groups. Compared with the LG group, the NACT group exhibit a smaller tumor size and significantly less advanced pathological tumor classification and nodal classification stages. The time to first flatus of the NACT group was significantly shorter, but the hospital stay was significantly longer than that of the LG group. The NACT group showed similar overall (29.3% vs 25.2%, P=0.683), systemic (24.4% vs 21.1%, P=0.663), local (12.2% vs 9.8%, P=0.767), minor (19.5% vs 19.5%, P=1.000) and major (9.8% vs 5.7%, P=0.470) complications as the LG group. Subgroup analyses showed no significant differences in most stratified parameters. Operation time≥ 300 minutes was identified as an independent risk factor for overall complications. Age≥ 60 years was identified as an independent risk factor for major complications. CONCLUSION: NACT combined with LG for AEG does not increase the risk of postoperative morbidity and mortality compared with LG.