Localization and delocalization of light in photonic moiré lattices.

Moiré lattices consist of two superimposed identical periodic structures with a relative rotation angle. Moiré lattices have several applications in everyday life, including artistic design, the textile industry, architecture, image processing, metrology and interferometry. For scientific studies, they have been produced using coupled graphene-hexagonal boron nitride monolayers1,2, graphene-graphene layers3,4 and graphene quasicrystals on a silicon carbide surface5. The recent surge of interest in moiré lattices arises from the possibility of exploring many salient physical phenomena in such systems; examples include commensurable-incommensurable transitions and topological defects2, the emergence of insulating states owing to band flattening3,6, unconventional superconductivity4 controlled by the rotation angle7,8, the quantum Hall effect9, the realization of non-Abelian gauge potentials10 and the appearance of quasicrystals at special rotation angles11. A fundamental question that remains unexplored concerns the evolution of waves in the potentials defined by moiré lattices. Here we experimentally create two-dimensional photonic moiré lattices, which-unlike their material counterparts-have readily controllable parameters and symmetry, allowing us to explore transitions between structures with fundamentally different geometries (periodic, general aperiodic and quasicrystal). We observe localization of light in deterministic linear lattices that is based on flat-band physics6, in contrast to previous schemes based on light diffusion in optical quasicrystals12, where disorder is required13 for the onset of Anderson localization14 (that is, wave localization in random media). Using commensurable and incommensurable moiré patterns, we experimentally demonstrate the two-dimensional localization-delocalization transition of light. Moiré lattices may feature an almost arbitrary geometry that is consistent with the crystallographic symmetry groups of the sublattices, and therefore afford a powerful tool for controlling the properties of light patterns and exploring the physics of periodic-aperiodic phase transitions and two-dimensional wavepacket phenomena relevant to several areas of science, including optics, acoustics, condensed matter and atomic physics.

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 locally advanced gastric cancer (LAGC). BACKGROUND: 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 noncompliance 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 noncompliance 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.

Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

SOX9 Modulates the Transformation of Gastric Stem Cells Through Biased Symmetric Cell Division.

BACKGROUND & AIMS: Transformation of stem/progenitor cells has been associated with tumorigenesis in multiple tissues, but stem cells in the stomach have been hard to localize. We therefore aimed to use a combination of several markers to better target oncogenes to gastric stem cells and understand their behavior in the initial stages of gastric tumorigenesis. METHODS: Mouse models of gastric metaplasia and cancer by targeting stem/progenitor cells were generated and analyzed with techniques including reanalysis of single-cell RNA sequencing and immunostaining. Gastric cancer cell organoids were genetically manipulated with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) for functional studies. Cell division was determined by bromodeoxyuridine-chasing assay and the assessment of the orientation of the mitotic spindles. Gastric tissues from patients were examined by histopathology and immunostaining. RESULTS: Oncogenic insults lead to expansion of SOX9+ progenitor cells in the mouse stomach. Genetic lineage tracing and organoid culture studies show that SOX9+ gastric epithelial cells overlap with SOX2+ progenitors and include stem cells that can self-renew and differentiate to generate all gastric epithelial cells. Moreover, oncogenic targeting of SOX9+SOX2+ cells leads to invasive gastric cancer in our novel mouse model (Sox2-CreERT;Sox9-loxp(66)-rtTA-T2A-Flpo-IRES-loxp(71);Kras(Frt-STOP-Frt-G12D);P53R172H), which combines Cre-loxp and Flippase-Frt genetic recombination systems. Sox9 deletion impedes the expansion of gastric progenitor cells and blocks neoplasia after Kras activation. Although Sox9 is not required for maintaining tissue homeostasis where asymmetric division predominates, loss of Sox9 in the setting of Kras activation leads to reduced symmetric cell division and effectively attenuates the Kras-dependent expansion of stem/progenitor cells. Similarly, Sox9 deletion in gastric cancer organoids reduces symmetric cell division, organoid number, and organoid size. In patients with gastric cancer, high levels of SOX9 are associated with recurrence and poor prognosis. CONCLUSION: SOX9 marks gastric stem cells and modulates biased symmetric cell division, which appears to be required for the malignant transformation of gastric stem cells.

Predictive Value of a New Muscle Parameter in Patients with Resectable Gastric Cancer: A Pooled Analysis of Three Prospective Trials.

BACKGROUND: Sarcopenia is closely associated with gastric cancer (GC) prognosis. However, its exact definition remains controversial. METHODS: This study included computed tomography images and clinical data of patients from three prospective studies. The skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SMRA) were analyzed, and a new muscle parameter, skeletal muscle gauge (SMG), was obtained by multiplying the two parameters. The values of the three indices for predicting the prognosis of patients with GC were compared. RESULTS: The study included 717 patients. The findings showed median values of 42 cm2/m2 (range, 36.8-48.2 cm2/m2) for SMI, 45 HU (range, 41-49 HU) for SMRA, and 1842 (range, 1454-2260) for SMG. Postoperatively, 111 patients (15.5%) experienced complications. The 3-year overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were 74.3%, 68.2%, and 70%, respectively. Univariate logistic analysis showed that postoperative complications were associated with SMI (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.92-0.96), SMRA (OR, 0.87; 95% CI 0.84-0.90), and SMG (OR 0.99; 95% CI 0.98-0.99). After a two-step multivariate analysis, only SMG (OR 0.98, 95% CI 0.97-0.99) was an independent protective factor of postoperative complications. Multivariate analysis showed that SMG also was an independent protective factor of OS, DFS, and RFS. The patients were divided into low-SMG (L-SMG) group and high-SMG (H-SMG) groups. Chemotherapy benefit analysis of the patients with stage II low SMG showed that the OS, DFS, and RFS of the chemotherapy group were significantly better than those of the non-chemotherapy group (p < 0.05). CONCLUSION: The prospective large sample data showed that the new muscle parameter, SMG, can effectively predict the short-term outcome and long-term prognosis of patients with resectable gastric cancer. As a new muscle parameter index, SMG is worthy of further study.

Comparison of Short-Term Outcomes After Robotic Versus Laparoscopic Radical Gastrectomy for Advanced Gastric Cancer in Elderly Individuals: A Propensity Score-Matching Study.

BACKGROUND: Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported. METHODS: The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM). RESULTS: After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02). CONCLUSIONS: For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy.

Trajectories of neutrophil-to-lymphocyte ratios during neoadjuvant chemotherapy correlate with short- and long-term outcomes in gastric cancer: a group-based trajectory analysis.

BACKGROUND: Systemic inflammatory factors can predict the survival prognosis of gastric cancer (GC) patients after neoadjuvant chemotherapy (NACT). However, whether longitudinal changes in systemic inflammatory factors are associated with short - and long-term outcomes has not been reported. METHODS: This study is a retrospective analysis of 216 patients with advanced gastric cancer who received NACT between January 2011 and June 2019, comparing receiver operating characteristic (ROC) curves for screening suitable inflammatory markers. Group-based trajectory modeling (GBTM) was used to analyze longitudinal changes in inflammatory markers during NACT to identify different potential subgroups and to compare postoperative complications, recurrence-free survival (RFS), and overall survival (OS) among subgroups. RESULTS: Ultimately, neutrophil-lymphocyte ratio (NLR) had the highest area under the curve (AUC) value in predicting prognosis was included in the GBTM analysis. Three trajectories of NLR were obtained: Stable group (SG) (n = 89), Ascent-descend group (ADG) (n = 80) and Continuous descend group (CDG) (n = 47). Compared with SG, ADG and CDG are associated with an increased risk of postoperative recurrence and death. The median time of RFS and OS of SG was longer than that of ADG and CDG (median RFS 81 vs. 44 and 22 months; median OS 69 vs. 41 and 30 months). In addition, CDG had significantly higher postoperative serious complications than SG and ADG (17 (36.2%) vs. 17 (19.1%) and 12 (15.0%); p = 0.005). CONCLUSION: There were different trajectories of NLR during NACT, and these potential trajectories were significantly associated with severe postoperative complications, recurrence, and mortality in patients with GC.

Impact of chemotherapy delay on long-term prognosis of laparoscopic radical surgery for locally advanced gastric cancer: a pooled analysis of four randomized controlled trials.

BACKGROUND: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II-III locally AGC and explore the associated risk factors. METHODS: Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established. RESULTS: In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II-III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets. CONCLUSION: Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II-III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.

Long-term oncological outcomes of 3D versus 2D laparoscopic gastrectomy for gastric cancer: a randomized clinical trial.

BACKGROUND: Laparoscopy-assisted gastrectomy (LG) is rapidly gaining popularity owing to its minimal invasiveness. Previous studies have found that compared with two-dimensional (2D)-LG, three-dimensional (3D)-LG showed better short-term outcomes. However, the long-term oncological outcomes in patients with locally resectable gastric cancer (GC) remain controversial. METHODS: In this noninferiority, open-label, randomized clinical trial, a total of 438 eligible GC participants were randomly assigned in a 1:1 ratio to either 3D-LG or 2D-LG from January 2015 to April 2016. The primary endpoint was operating time, while the secondary endpoints included 5-year overall survival (OS), disease-free survival (DFS), and recurrence pattern. RESULTS: Data from 401 participants were included in the per-protocol analysis, with 204 patients in the 3D group and 197 patients in the 2D group. The 5-year OS and DFS rates were comparable between the 3D and 2D groups (5-year OS: 70.6% vs. 71.1%, Log-rank P = 0.743; 5-year DFS: 68.1% vs. 69.0%, log-rank P = 0.712). No significant differences were observed between the 3D and 2D groups in the 5-year recurrence rate (28.9% vs. 28.9%, P = 0.958) or recurrence time (mean time, 22.6 vs. 20.5 months, P = 0.412). Further stratified analysis based on the type of gastrectomy, postoperative pathological staging, and preoperative BMI showed that the 5-year OS, DFS, and recurrence rates of the 3D group in each subgroup were similar to those of the 2D group (all P > 0.05). CONCLUSIONS: For patients with locally resectable GC, 3D-LG performed by experienced surgeons in high-volume professional institutions can achieve long-term oncological outcomes comparable to those of 2D-LG. REGISTRATION NUMBER: NCT02327481 ( http://clinicaltrials.gov ).

Appraisal of surgical outcomes and oncological efficiency of intraoperative adverse events in robotic radical gastrectomy for gastric cancer.

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

Robotic gastrectomy was reliable option for overweight patients with gastric cancer: a propensity score matching study.

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

Effect of sarcopenia on short-term and long-term outcomes of older patients with locally advanced gastric cancer: a multicenter study.

OBJECTIVE: To assess the effect of preoperative sarcopenia on the short-term and long-term outcomes in older patients with locally advanced gastric cancer (LAGC). METHODS: Clinicopathological data of older patients with LAGC who underwent radical surgery were retrospectively analyzed. Sarcopenia was defined as a skeletal muscle index of less than 36.4 cm2/m2 for men and less than 28.4 cm2/m2 for women. Comparing the postoperative complications and survival between sarcopenia and non-sarcopenia groups using multicenter data. RESULTS: A total of 406 older patients with LAGC were included in the analysis, including 145 (35.7%) with sarcopenia and 261 (64.3%) with non-sarcopenia. Multivariate logistic regression analysis showed that sarcopenia was an independent risk factor for postoperative complications with CD grade ≥ II (OR 1.616; P < 0.05). Kaplan-Meier survival curve analysis showed that the 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) in the sarcopenia group were lower than those in the non-sarcopenia group (P both < 0.05). Multivariate Cox regression analyses showed that sarcopenia was an independent prognostic factor for 5-year OS and RFS (P both < 0.05). The 5-year recurrence rate in the sarcopenia group was 57.2%, which was significantly higher than that in the non-sarcopenia group (46.4%; P = 0.036). Recurrence pattern analysis showed that the incidence of distant metastases in patients with sarcopenia (42.8%) was significantly higher than non-sarcopenia (31.4%; P = 0.022). CONCLUSION: Sarcopenia serves as a valuable predictor of both short-term and long-term outcomes in older patients with LAGC. Therefore, the significance of assessing preoperative nutritional status and implementing thorough postoperative follow-up for older LAGC patients with sarcopenia should be emphasized.

Robot-assisted versus laparoscopic-assisted gastrectomy among malnourished patients with gastric cancer based on textbook outcome.

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

Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035.

OBJECTIVE: To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. METHODS: Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex. RESULTS: More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5-2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6-5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20-44, Thailand [AAPC, 3.4; (95%cl, 1.3-5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035. CONCLUSION: In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45 years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth.

Intraoperative Adverse Events, Technical Performance, and Surgical Outcomes in Laparoscopic Radical Surgery for Gastric Cancer: A Pooled Analysis From 2 Randomized Trials.

OBJECTIVE: To verify an intraoperative adverse event (iAE) classification (ClassIntra grade) to evaluate quality control and to predict the prognostic performance of laparoscopic radical surgery for gastric cancer. BACKGROUND: Surgical quality control is a key factor in the evaluation of surgical treatment for tumors. And, there is no recognized iAE classification for gastric cancer. METHODS: We performed a retrospective post hoc analysis of previously collected data from the FUGES-001 study (NCT02327481) and a subset of the CLASS-01 study (NCT01609309). Patients were classified into the iAE and non-iAE groups. And iAE was further classified into 5 subgrades according to the ClassIntra grade (with I-V severity categories). Technical performance was evaluated using the Objective Structured Assessment of Technical Skills tool and the Generic Error Rating Tool. RESULTS: Overall, 528 gastric cancer patients were included in this study, with 105 patients (19.9%) in the iAE group and 423 (80.1%) in the non-iAE group. The survival curve showed that the overall, disease-specific, and recurrence-free survival of the non-iAE group were significantly better than those of the iAE group ( P =0.001). The prognosis of patients with ClassIntra grade ≥II was significantly worse than that of patients with ClassIntra grade ≤I. A higher ClassIntra grade, lower Objective Structured Assessment of Technical Skills score, and total gastrectomy were independent risk factors for severe postoperative complications. There was a significant increase in bleeding (grade IV) and injury with splenic hilar lymph node dissection during total gastrectomy. CONCLUSIONS: The ClassIntra grade is an effective prognostic and surgical quality control index for laparoscopic radical surgery for gastric cancer; therefore, it could be included in routine hospital care and surgical quality control.

Helicobacter pylori-induced RASAL2 Through Activation of Nuclear Factor-κB Promotes Gastric Tumorigenesis via ß-catenin Signaling Axis.

BACKGROUND & AIMS: Helicobacter pylori infection is the predominant risk factor for gastric cancer. RAS protein activator like 2 (RASAL2) is considered a double-edged sword in carcinogenesis. Herein, we investigated the role of RASAL2 in response to H pylori infection and gastric tumorigenesis. METHODS: Bioinformatics analyses of local and public databases were applied to analyze RASAL2 expression, signaling pathways, and clinical significance. In vitro cell culture, spheroids, patient-derived organoids, and in vivo mouse models were used. Molecular assays included chromatin immunoprecipitation, co-immunoprecipitation, Western blotting, quantitative polymerase chain reaction, and immunocyto/histochemistry. RESULTS: H pylori infection induced RASAL2 expression via a nuclear factor-κB (NF-κB)-dependent mechanism whereby NF-κB was directly bound to the RASAL2 promoter activating its transcription. By gene silencing and ectopic overexpression, we found that RASAL2 upregulated ß-catenin transcriptional activity. RASAL2 inhibited protein phosphatase 2A activity through direct binding with subsequent activation of the AKT/ß-catenin signaling axis. Functionally, RASAL2 silencing decreased nuclear ß-catenin levels and impaired tumor spheroids and organoids formation. Furthermore, the depletion of RASAL2 impaired tumor growth in gastric tumor xenograft mouse models. Clinicopathological analysis indicated that abnormal overexpression of RASAL2 correlated with poor prognosis and chemoresistance in human gastric tumors. CONCLUSIONS: These studies uncovered a novel signaling axis of NF-κB/RASAL2/ß-catenin, providing a novel link between infection, inflammation and gastric tumorigenesis.

Value of the Preoperative D-Dimer to Albumin Ratio for Survival and Recurrence Patterns in Gastric Cancer.

BACKGROUND: D-dimer (DDI) and albumin are prognostic markers for numerous cancers; however, the predictive value of the preoperative DDI-to-albumin ratio (DAR) on the survival and recurrence patterns of gastric cancer (GC) remains unclear. OBJECTIVE: The aim of this study was to explore the prognostic value of the DAR in GC. METHODS: Our study included 1766 patients with GC, divided into training and testing cohorts at a ratio of 7:3. Patients were classified into either a high-DAR group (> 0.0145) or low-DAR group (≤ 0.0145) according to the cut-off value of receiver operating characteristic (ROC) curve analysis. The relationship between the DAR and recurrence pattern was analyzed in stage II/III patients. RESULTS: Eight preoperative hematological factors were included and 17 composite inflammatory markers were constructed. ROC and random forest analyses indicated that among 17 markers, DAR was the best predictor for overall survival (OS) in GC (p < 0.01). High DAR was significantly associated with poor OS (hazard ratio [HR] 1.89, p < 0.001) and recurrence-free survival (RFS; HR 1.85, p < 0.001). Subgroup analysis showed no differences in OS and RFS between the high- and low-DAR groups in stage I or pT1/2 or pN0/1 patients; however, in stage II/III or pT3/4 or pN2/3 patients, the high-DAR group had shorter OS and RFS rates than the low-DAR group (p < 0.001). Similar results were found in the testing cohort. According to the multivariate analysis based on the training cohort, five indices, including DAR, cT stage, cN stage, age and body mass index (BMI), were incorporated to establish a nomogram model to predict the long-term prognosis of GC. The model showed comparable forecast performance in predicting OS (C-index: 0.773 vs. 0.786) and RFS (C-index: 0.788 vs. 0.795) compared with pTNM. Recurrence pattern analysis in stage II/III patients showed that the high-DAR group had a higher incidence of peritoneal implantation and early recurrence (ER) than the low-DAR group, and the post-recurrence survival in the high-DAR group was significantly shorter than that in the low-DAR group (p = 0.016). CONCLUSION: The preoperative DAR is a new biomarker for the long-term survival prediction of GC. In advanced GC, a preoperative DAR > 0.0145 aids the timely detection of ER and peritoneal recurrence after surgery, thus guiding individual follow-up strategies.

Patient-Reported Outcomes of Individuals with Gastric Cancer Undergoing Totally Laparoscopic Versus Laparoscopic-Assisted Total Gastrectomy: A Real-World, Propensity Score-Matching Analysis.

OBJECTIVE: Totally laparoscopic total gastrectomy (TLTG) and laparoscopic-assisted total gastrectomy (LATG) are two types of minimally invasive radical gastrectomy procedures to treat gastric cancer (GC). This study compared the long-term prognosis and postoperative health-related quality of life (HRQoL) between TLTG and LATG. METHODS: A total of 106 patients who underwent TLTG and 1,076 patients who underwent LATG at the Union Hospital of Fujian Medical University (Fuzhou, China) between January 2014 and April 2018 were included in the propensity score matching (PSM, 1:2). Patient-reported outcomes at 3, 6, and 12 months after gastrectomy were analyzed. The questionnaire referred to the European Organization for Research and Treatment of Cancer (EORTC) 30-item core QoL (QLQ-C30)and the GC module (QLQ-STO22) questionnaire. RESULTS: After PSM, there were no significant differences in clinicopathological characteristics between the TLTG (n = 104) and the LATG groups (n = 208). Operative time and volume of blood loss were significantly lower in the TLTG group than in the LATG group. Kaplan-Meier survival analysis revealed similar 3-year survival rates between the TLTG and LATG groups (83.7 vs. 80.3%, respectively; P = 0.462). Tolerance to nonliquid diet, decrease in body weight, and albumin levels were also significantly lower in the TLTG group than in the LATG group (all P < 0.05). The HRQoL scale demonstrated that the overall score in the TLTG group was better than that in the LATG group at 3, 6, and 12 months after gastrectomy (all P < 0.05). CONCLUSIONS: Patients with GC undergoing TLTG reported better HRQoL and experienced faster recovery of social function than those undergoing LATG, although the two groups demonstrated similar short-term outcomes and long-term prognosis.

Nomogram to Predict Recurrence and Guide a Pragmatic Surveillance Strategy After Resection of Hepatoid Adenocarcinoma of the Stomach: A Retrospective Multicenter Study.

BACKGROUND: An accurate recurrence risk assessment system and surveillance strategy for hepatoid adenocarcinoma of the stomach (HAS) remain poorly defined. This study aimed to develop a nomogram to predict postoperative recurrence of HAS and guide individually tailored surveillance strategies. METHODS: The study enrolled all patients with primary HAS who had undergone curative-intent resection at 14 institutions from 2004 to 2019. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram to build a recurrence predictive model. RESULTS: The nomogram of recurrence-free survival (RFS) based on independent prognostic factors, including age, preoperative carcinoembryonic antigen, number of examined lymph nodes, perineural invasion, and lymph node ratio, achieved a C-index of 0.723 (95% confidence interval [CI], 0.674-0.772) in the whole cohort, which was significantly higher than those of the eighth American Joint Committed on Cancer (AJCC) staging system (C-index, 0.629; 95% CI, 0.573-0.685; P < 0.001). The nomogram accurately stratified patients into low-, middle-, and high-risk groups of postoperative recurrence. The postoperative recurrence risk rates for patients in the middle- and high-risk groups were respectively 3 and 10 times higher than for the low-risk group. The patients in the middle- and high-risk groups showed more recurrence and metastasis, particularly multiple site metastasis, within 36 months after the operation than those in the low-risk group (low, 2.2%; middle, 8.6%; high, 24.0%; P = 0.003). CONCLUSIONS: The nomogram achieved good prediction of postoperative recurrence for the patients with HAS after radical resection. For the middle- and high-risk patients, more active surveillance and targeted examination methods should be adopted within 36 months after the operation, particularly for liver and multiple metastases.

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.