Dynamic RNA methylation modifications and their regulatory role in mammalian development and diseases.

Among over 170 different types of chemical modifications on RNA nucleobases identified so far, RNA methylation is the major type of epitranscriptomic modifications existing on almost all types of RNAs, and has been demonstrated to participate in the entire process of RNA metabolism, including transcription, pre-mRNA alternative splicing and maturation, mRNA nucleus export, mRNA degradation and stabilization, mRNA translation. Attributing to the development of high-throughput detection technologies and the identification of both dynamic regulators and recognition proteins, mechanisms of RNA methylation modification in regulating the normal development of the organism as well as various disease occurrence and developmental abnormalities upon RNA methylation dysregulation have become increasingly clear. Here, we particularly focus on three types of RNA methylations: N6-methylcytosine (m6A), 5-methylcytosine (m5C), and N7-methyladenosine (m7G). We summarize the elements related to their dynamic installment and removal, specific binding proteins, and the development of high-throughput detection technologies. Then, for a comprehensive understanding of their biological significance, we also overview the latest knowledge on the underlying mechanisms and key roles of these three mRNA methylation modifications in gametogenesis, embryonic development, immune system development, as well as disease and tumor progression.

Evaluation of factors influencing long-term and textbook outcomes in laparoscopic gastrectomy.

BACKGROUND: Textbook outcome (TO) in gastric cancer surgery is a multidimensional measure of surgical quality. However, its impact on long-term survival after laparoscopic gastrectomy (LG) is unclear. This study aims to evaluate TO in LG, assess its hospital-level relevance, and examine its association with long-term survival. METHODS: In this retrospective cohort study, we analyzed 2278 consecutive gastric cancer patients who underwent laparoscopic gastrectomy (LG) from January 2004 to December 2017. We determined TO achievement rates, compared preoperative and intraoperative variables between TO and non-TO groups, identified independent predictors of TO, and assessed long-term oncologic outcomes using Kaplan-Meier analysis and Cox regression. RESULTS: A total of 1540 LG patients were analyzed, with 994 (64.5%) achieving TO. The least frequently achieved metric was 'hospital stays ≤21 days' (83.4%), followed by 'lymph nodes retrieved ≥15' (84.0%). Factors independently associated with reduced TO likelihood included age ≥65 years, BMI ≥25, ASA III, conversion to open surgery, operation time ≥260 min, and estimated blood loss ≥150 ml. Furthermore, TO was independently linked to improved 5-year overall survival (OS) and disease-free survival (DFS) (HR 0.519 [0.443-0.609] and HR 0.517 [0.443-0.604], respectively). CONCLUSION: Implementing the TO concept in LG provides a benchmark for achieving improved prognoses and empowers surgeons to devise strategies for enhancing surgical care quality.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS: In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS: The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION: Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

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.

RBM10 regulates the tumorigenic potential of human cancer cells by modulating PPM1B and YBX1 activities.

RNA binding protein RBM10 participates in various RNA metabolism, and its decreased expression or loss of function by mutation has been identified in many human cancers. However, how its dysregulation contributes to human cancer pathogenesis remains to be determined. Here, we found that RBM10 expression was decreased in breast tumors, and breast cancer patients with low RBM10 expression presented poorer survival rates. RBM10 depletion in breast cancer cells significantly promotes the cellular proliferation and migration. We further demonstrated that RBM10 forms a triple complex with YBX1 and phosphatase 1B (PPM1B), in which PPM1B serves as the phosphatase of YBX1. RBM10 knock-down markedly attenuated association between YBX1 and PPM1B, leading to elevated levels of YBX1 phosphorylation and its nuclear translocation. Furthermore, cancer cells with RBM10 depletion had a significantly accelerated tumor growth in nude mice. Importantly, these enhanced tumorigenic phenotypes can be reversed by overexpression of PPM1B. Our findings provide the mechanistic bases for functional loss of RBM10 in promoting tumorigenicity, and are potentially useful in the development of combined therapeutic strategies for cancer patients with defective RBM10.

Tumor-infiltrating mast cells stimulate ICOS+ regulatory T cells through an IL-33 and IL-2 axis to promote gastric cancer progression.

INTRODUCTION: In solid tumors, regulatory T cell (Treg) and mast cell perform different roles depending on the microenvironment. Nevertheless, mast cell and Treg-mediated interactions in gastric cancer (GC) are unclear, as are their regulation, function, and clinical significance. OBJECTIVE: The present study demonstrated the mechanism of tumor-infiltrating mast cells stimulating ICOS+ regulatory T cells via the IL-33/IL-2 axis to promote the growth of gastric cancer. METHODS: Analyses of 98 patients with GC were conducted to examine mast cell counts, ICOS+ Tregs, and the levels of IL-33 or IL-2. Isolated ICOS+ Treg and CD8+ T cell were stimulated, cultured and tested for their functional abilities in vitro and in vivo. RESULTS: GC patients exhibited a significantly more production of IL-33 in tumors. Mast cell stimulated by tumor-derived IL-33 exhibited a prolonged lifespan through IL-33 mediated inhibition of apoptosis. Moreover, mast cells stimulated by tumor-derived IL-33 secreted IL-2, which induced Treg expansion. These inducible Tregs displayed an activated immunosuppressive phenotype with positive expression for the inducible T cell co-stimulator (ICOS). In vitro, IL-2 from IL to 33-stimulated mast cells induced increased numbers of ICOS+ Tregs with increased immunosuppressive activity against proliferation and effector function of CD8+ T cell. In vivo, ICOS+ Tregs were treated with anti-IL-2 neutralizing antibody followed by co-injection with CD8+ T cells in GC mouse model, which showed an increased CD8+ T cell infiltration and effector molecules production, meanwhile tumor growth and progression were inhibited. Besides, reduction in GC patient survival was associated with tumor-derived ICOS+ Tregs. CONCLUSION: Our results highlight a crosstalk between GC-infiltrating mast cells and ICOS+ Tregs and provide a novel mechanism describing ICOS+ Treg expansion and induction by an IL-33/mast cell/IL-2 signaling axis in GC, and also provide functional evidence that the modulation of this immunosuppressive pathway can attenuate GC-mediated immune tolerance.

Total versus proximal gastrectomy for proximal gastric cancer after neoadjuvant chemotherapy: a multicenter retrospective propensity score-matched cohort study.

BACKGROUND: This study aimed to analyze and compare the short-term and long-term outcomes of proximal gastrectomy (PG) and total gastrectomy (TG) in patients with locally advanced proximal gastric cancer (GC) following neoadjuvant chemotherapy (NACT). METHOD: A multicenter retrospective cohort study and propensity score matching (PSM) were employed. The authors examined 367 patients with proximal GC who received NACT followed by PG ( n =164) or TG ( n =203) at two Chinese medical institutions between December 2009 and December 2022. Clinical and pathological parameters, postoperative complications, and 5-year overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. The dissection status and metastasis rate of each lymph node station were assessed. RESULTS: After PSM, 80 patients were enrolled in both TG and PG group, and baseline characteristics were comparable between the groups (all P >0.05). The TG group had a higher total number of lymph nodes retrieved ( P <0.001) and longer operative time ( P =0.007) compared to the PG group. The incidence of Clavien-Dindo grade II or higher postoperative complications was similar between the TG group (21.3%, 17/80) and the PG group (17.5%, 14/80) ( P =0.689). The 5-year OS rates were 68.4 for the PG group and 66.0% for the TG group ( P =0.881), while the 5-year RFS rates were 64.8 and 61.9%, respectively ( P =0.571), with no statistically significant differences. Metastasis rates at lymph node stations #4d, #5, #6, and #12a were notably low in the TG group, with values of 2.74, 0.67, 1.33, and 1.74%, respectively. CONCLUSION: For proximal GC patients following NACT, PG maintains comparable curative potential and oncological efficacy to TG, making it a safe option.

Effect of bladder filling status on positioning errors in post-hysterectomy cervical cancer radiotherapy.

Objective: To investigate the effect of different bladder filling states on positioning errors in radiotherapy for cervical cancer and obtain the reference range of bladder filling consistency during radiotherapy.Methods: Patients who underwent postoperative radiotherapy for cervical cancer in Nantong Tumor Hospital from October 2018 to December 2019 were selected. According to the bladder filling deviation, they were divided into group A1 (deviation < 20%) and group B1 (deviation ≥ 20%). The bladder filling variations of the two groups were compared with different positioning errors. Group A2 has a positioning error of <0.4 cm, and group B2 has a positioning error of ≥0.4 cm. The reference range of bladder filling consistency during radiotherapy is obtained by analyzing the composition ratio of different positioning errors of bladder filling deviation.Results: This study included 195 patients with cervical cancer. The error of longitudinal and vertical position in group B1 was significantly higher than that in group A1 (0.50 ± 0.34 vs. 0.26 ± 0.22 cm, p < 0.001, and 0.22 ± 0.17 vs. 0.16 ± 0.12 cm, p < 0.001). Compared with group B2, the absolute deviation of bladder filling in group A2 (54.1% ± 54.4% vs. 25.6% ± 22.7%, p < 0.001) was slight. The chi-square test showed significant differences in the proportion of the positioning state of different bladder filling forms (χ2 = 31.006, p < 0.001). In addition, there was a significant difference in the proportion of stability errors in patients with poor stability in different directions (χ2 = 118.551, p < 0.001).Conclusion: In patients with cervical cancer fixed in the supine position, a bladder capacity deviation <20% is easier to achieve excellent positioning with, and it can better control the positioning error of radiotherapy and ensure the positioning accuracy of dose distribution to the target area. It can also achieve good tumor treatment effects. This range can be used as a reference for bladder filling consistency in patients with cervical cancer undergoing radiotherapy.

Long-term oncologic and surgical outcomes of robotic and laparoscopic gastrectomy for Siewert II/III esophagogastric junction carcinoma: A propensity score-matched retrospective cohort study.

BACKGROUND: This study aimed to investigate the short-term surgical and long-term survival outcomes after robotic gastrectomy (RG) or laparoscopic gastrectomy (LG) for patients with Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). METHODS: We retrospectively analyzed 84 and 312 patients with Siewert type II/III AEG who underwent RG or LG between January 2005 and September 2016 in our center. We performed a 1:2 matched propensity score matching (PSM) analysis between the RG and LG group for clinical features to reduce confounding bias. Additionally, the long- and short-term outcomes between the RG and LG group were compared. RESULTS: The clinicopathological characteristics of 246 patients (RG group: n = 82; LG group: n = 164) were well balanced after PSM. Patients in the RG group showed less estimated blood loss, less time to first flatus, less time to first ambulation, less drainage tube removed time, and retrieved more lymph nodes than the LG group. The overall complication rate was comparable between the RG and LG groups. The 5-year overall survival (OS) was 44.4% in the RG group and 43.7% in the LG group (p = 0.898). The 5-year disease-free survival (DFS) was 43.2% in the RG group and 43.2% in the LG group (p = 0.990). The RG and LG groups exhibited a similar recurrence rate and pattern within 5 years after surgery. CONCLUSION: Robotic gastrectomy could be a feasible and safe option for patients with Siewert II/III AEG in terms of surgical and oncologic outcomes.

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.

A comparative study on perioperative outcomes between robotic versus laparoscopic D2 total gastrectomy.

OBJECTIVE: Robotic surgery has been increasingly used worldwide owing to its advanced features. However, the significant benefits of robotic total gastrectomy (RTG) over laparoscopic total gastrectomy (LTG) have yet to be demonstrated. We conducted a prospective cohort study to compare the safety and efficacy of robotic and laparoscopic total gastrectomy (LTG) with D2 lymphadenectomy for AGC. METHODS: Between March 26, 2018 and July 30, 2021, 155 patients between 18 and 80 years of age with locally advanced gastric cancer (cT2-4a, N0/+, M0) were enrolled. The perioperative outcomes within 30 days after surgery were compared between the RTG (n = 69) and LTG (n = 73) groups on a per-protocol (PP) basis. Postoperative complications were evaluated according to the Clavien-Dindo classification. RESULTS: The overall postoperative morbidity rate was 21.74% in the RTG group and 28.77% in the LTG group with no significant difference (P = 0.44), RTG was associated with a lower incidence of pneumonia (4.35% vs. 15.07%, P = 0.047). No mortality was observed in either group. There was no significant difference in the total operative time (284.48 vs. 271.73 min, P = 0.171), but RTG was associated with a lower estimated volume of blood loss (110 vs. 150 ml, P < 0.001) and more total retrieved lymph nodes (LNs) (41.36 vs 35.1, P = 0.019), more extraperigastric LNs (14.91 vs. 12.19, P = 0.024) and more LNs in the suprapancreatic areas (14.68 vs. 11.82, P = 0.017). The laboratory data (amylase, inflammatory, Albumin and T lymphocyte levels) of the RTG group were better than those of the LTG group. CONCLUSION: According to the results of this prospective cohort study, for patients with locally advanced gastric cancer, Robotic surgery has advantages over laparoscopic surgery for radical total gastrectomy with D2 lymphadenectomy performed by well-trained doctors.

Micropeptide PACMP inhibition elicits synthetic lethal effects by decreasing CtIP and poly(ADP-ribosyl)ation.

Synthetic lethality through combinatorial targeting DNA damage response (DDR) pathways provides exciting anticancer therapeutic benefit. Currently, the long noncoding RNAs (lncRNAs) have been implicated in tumor drug resistance; however, their potential significance in DDR is still largely unknown. Here, we report that a human lncRNA, CTD-2256P15.2, encodes a micropeptide, named PAR-amplifying and CtIP-maintaining micropeptide (PACMP), with a dual function to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. PACMP not only prevents CtIP from ubiquitination through inhibiting the CtIP-KLHL15 association but also directly binds DNA damage-induced poly(ADP-ribose) chains to enhance PARP1-dependent poly(ADP-ribosyl)ation. Targeting PACMP alone inhibits tumor growth by causing a synthetic lethal interaction between CtIP and PARP inhibitions and confers sensitivity to PARP/ATR/CDK4/6 inhibitors, ionizing radiation, epirubicin, and camptothecin. Our findings reveal that a lncRNA-derived micropeptide regulates cancer progression and drug resistance by modulating DDR, whose inhibition could be employed to augment the existing anticancer therapeutic strategies.

Incidence and risk factors for postoperative pancreatic fistula in 2089 patients treated by radical gastrectomy: A prospective multicenter cohort study in China.

OBJECTIVE: To determine the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) following radical gastrectomy and to identify independent risk factors of CR-POPF. BACKGROUND: CR-POPF and its sequelae are potential complications following radical gastrectomy. The reported incidence of CR-POPF was quite different across various regions, and no consensus was reached. METHODS: Between December 2017 to November 2018, patients who underwent radical gastrectomy from 22 centers across 13 regions in China were prospectively recruited. The primary endpoint was the occurrence of CR-POPF, defined by the International Study Group of Pancreatic Fistula (ISGPF) in 2016. Clinically relevant change and short-term outcomes were recorded to diagnose and grade the POPF. Multivariate regression analyses were performed to identify independent risk factors of clinically relevant postoperative pancreatic fistula (CR-POPF). RESULTS: A total of 2089 cases were analyzed. The incidence of biochemical leakage (BL) and CR-POPF were 19.6% and 1.1% respectively. All CR-POPF patients recovered well after appropriate treatment and no Grade C POPF were recorded. Logistic regression analysis showed pTNM III (OR, 2.940; 95% CI 1.180-7.325; P = 0.021) and LigaSure usage (OR, 6.618; 95% CI 1.847-23.707; P = 0.004) were independent risk factors of CR-POPF. LigaSure usage (OR, 4.817; 95% CI 1.184-19.598; P = 0.028), the drain amylase content (D-AMY) on postoperative day 3 (POD3) ≥5 times the upper limit of normal amylase (OR, 3.476; 95% CI 1.240-9.744; P = 0.018) and open surgery (OR, 2.463; 95% CI 1.003-6.050; P = 0.049) were independent predictors for identifying CR-POPF from BL. CONCLUSION: In rich-experienced gastric cancer centers, there is high prevalence of BL secondary to radical gastrectomy without clinical impact. Fewer patients suffered Grade B POPF, and Grade C POPF was less common. The patients with pTNM III or LigaSure usage were prone to suffer CR-POPF. Surgery procedure, LigaSure usage combined with D-AMY measurement on POD3 are promising for early identification of CR-POPF.

FasL+ PD-L2+ Identifies a Novel Immunosuppressive Neutrophil Population in Human Gastric Cancer That Promotes Disease Progression.

Neutrophils constitute abundant cellular components in human gastric cancer (GC) tissues, but their protumorigenic subset in pathogenesis of GC progression is unclear. Here, it is found that patients with GC show significantly higher neutrophil infiltration in tumors that is regulated by CXCL12-CXCR4 chemotaxis. These tumor-infiltrating neutrophils express high level immunosuppressive molecules FasL and PD-L2, and this FasL+ PD-L2+ neutrophil subset with a unique phenotype constitutes at least 20% of all neutrophils in advanced GC and predicts poor patient survival. Tumor induces neutrophils to express FasL and PD-L2 proteins with similar phenotype to those in GC tumors in both time-dependent and dose-dependent manners. Mechanistically, Th17 cell-derived IL-17A and tumor cell-derived G-CSF can significantly induce neutrophil FasL and PD-L2 expression via activating ERK-NF-κB and JAK-STAT3 signaling pathway, respectively. Importantly, upon over-expressing FasL and PD-L2, neutrophils acquire immunosuppressive functions on tumor-specific CD8+ T-cells and promote the growth and progression of human GC tumors in vitro and in vivo, which can be reversed by blocking FasL and PD-L2 on these neutrophils. Thus, the work identifies a novel protumorigenic FasL+ PD-L2+ neutrophil subset in GC and provides new insights for human cancer immunosuppression and anti-cancer therapies targeting these pathogenic cells.

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.

Distribution, phenotype, functional and clinical relevance of CD8+CD103+ tissue-resident memory T cells in human gastric cancer.

CD8+CD103+ tissue-resident memory T cells (TRMs) are involved in tumor immune response and linked to favorable clinical outcome in human cancer. However, the distribution, phenotype, functional properties and clinical relevance of these cells in gastric cancer (GC) remain elusive. Here, our data show that, in comparison to non-tumor tissues, the percentages of CD8+CD103+ TRMs in tumors are significantly decreased. Most tumor-infiltrating CD8+CD103+ TRMs are CD45RA-CCR7- effector-memory cells with higher PD-1 and 4-1BB expression than those from non-tumor tissues. Further, tumor-infiltrating CD8+CD103+ TRMs show impaired cytolytic capacity due to decreased granzyme B and perforin expression. Moreover, ex vivo PD-1 blockade could restore the cytolytic capacity of tumor-infiltrating CD8+CD103+ TRMs, and such anti-PD-1-mediated reinvigoration of CD8+CD103+ TRMs could be further enhanced by 4-1BB co-stimulation. Finally, lower levels of Tumor-infiltrating CD8+CD103+ TRMs are positively correlated with GC progression and poor patients' survival. Our data suggest that restoring CD8+CD103+ TRM function by combining PD-1 blockade and 4-1BB co-stimulation may be a promising strategy for treating GC.

Surgical and survival outcomes after laparoscopic and open gastrectomy for serosa-invasive Siewert type II/III esophagogastric junction carcinoma: a propensity score matching analysis.

BACKGROUND: The potential advantage of laparoscopic gastrectomy (LG) compared with open gastrectomy (OG) for serosa-invasive (pT4a) Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG) remains uncertain. Thus, the purpose of this study was to investigate the short- and long-term outcomes of LG compared to OG for pT4a Siewert type II/III AEG cancers. METHODS: We retrospectively evaluated 283 patients with pathological confirmed T4a Siewert type II and type III AEG who underwent LG or OG in our center between January 2004 and September 2015. The short- and long-term outcomes were compared between the groups using a 1:1 matched propensity score matching method (PSM). RESULTS: The LG group had a longer operation time, less estimated blood loss, less time to first flatus, less time to start liquid diet, less time to first ambulation, and shorter length of incision than the OG group. The conversion rates were 5.4% in the LG groups. There was no significant difference in the overall complication rate between the LG and OG groups. The 5-year overall survival (OS) and the 5-year disease-free survival (DFS) were comparable between the LG and OG groups (35.4% vs 32.1%, p = 0.541; 34.1% vs 31.0%, p = 0.523, respectively). There was no significant difference in the recurrence rate and pattern between the LG and OG groups. CONCLUSIONS: Laparoscopic gastrectomy is associated with better short-term outcomes and similar long-term outcomes for pT4a Siewert type II/III AEG. This study reveals that LG could be a safe and feasible option for pT4a Siewert type II/III AEG compared to OG.

Survival Benefit of Pyloric Lymph Node Dissection for Siewert Type II/III Adenocarcinoma of the Esophagogastric Junction Based on Tumor Diameter: A Large Cohort Study.

BACKGROUND: It is unclear whether the dissection of pyloric lymph nodes (PLNs, No. 5 and No. 6 lymph nodes) is necessary for adenocarcinoma of the esophagogastric junction (AEG) with a tumor diameter >4 cm based on current guidelines. This study aimed at evaluating whether pyloric node lymphadenectomy is essential for patients with Siewert type II/III AEG according to different tumor diameters. METHODS: This study included 300 patients on whom transabdominal total gastrectomy was performed for Siewert type II/III AEG at a high-volume center in China from January 2006 to December 2015. The index of estimated benefit from lymph node dissection (IEBLD) was used to analyze the priority of pyloric lymphadenectomy. RESULTS: In Siewert type II AEG, the 5-year overall survival (OS) and the 5-year disease-free survival (DFS) were similar between patients with PLN-positive cancer and patients of stage III AEG without PLN metastasis (23.1% vs. 30.6%, p = 0.505; 23.1% vs. 27.1%, p = 0.678). However, in Siewert type III AEG, the OS and the DFS of patients with PLN-positive cancer were significantly lower than that of patients with stage III without PLN metastasis (7.9% vs. 27.8%, p = 0.021; 0 vs. 26.8%, p = 0.005). According to the IEBLD, the dissection of PLNs did not appear to be beneficial in either Siewert type II AEG or type III AEG, whereas a stratified analysis revealed that PLN dissection yielded a high therapeutic benefit for Siewert type II AEG with tumor diameters >4 cm. CONCLUSION: We recommended that the PLNs be dissected in Siewert type II AEG when a tumor diameter is >4 cm. Total gastrectomy should be optional for Siewert type II AEG with a tumor diameter >4 cm and Siewert type III AEG.

Robotic total gastrectomy for carcinoma in the remnant stomach: a comparison with laparoscopic total gastrectomy.

BACKGROUND: Total gastrectomy for carcinoma in the remnant stomach (CRS) remains a technically demanding procedure. Whether robotic surgery is superior, equal, or inferior to laparoscopic surgery in patients with CRS is unclear. This study was designed to compare the efficacy and safety of robotic total gastrectomy (RTG) and laparoscopic total gastrectomy (LTG) for the treatment of CRS. METHODS: In this cohort study, we retrospectively analysed the data from patients who underwent RTG or LTG for CRS at Southwest Hospital (Chongqing, China) between May 2006 and October 2019. The surgical outcomes, post-operative complications, and survival outcomes between the two groups were compared. RESULTS: Compared with LTG, RTG was associated with similar effective operation time (272.0 vs 297.9 min, P = 0.170), higher total costs (105,967.2 vs 81,629.5 RMB, P < 0.001), and less estimated blood loss (229.2 vs 288.8 mL, P = 0.031). No significant differences were found between the robotic and laparoscopic groups in terms of conversion rate, time to first flatus, time to first soft diet, post-operative hospital stay, post-operative complications, R0 resection rate, and number of retrieved lymph nodes (all P > 0.05). The 3-year disease-free survival and 3-year overall survival rates were comparable between the two groups (65.5% vs 57.5%, P = 0.918; 69.0% vs 60.0%, P = 0.850, respectively). CONCLUSIONS: RTG is a safe and feasible procedure for the treatment of CRS and could serve as an optimal treatment for CRS.

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.