The AP-2 Family of Transcription Factors-Still Undervalued Regulators in Gastroenterological Disorders.

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/ß/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2ß and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.

Helicobacter pylori eradication following endoscopic resection might prevent metachronous gastric cancer: a systematic review and meta-analysis of studies from Japan and Korea.

Objectives: A systematic review and meta-analysis was performed to evaluate the preventive effectiveness of Helicobacter pylori eradication against metachronous gastric cancer (MGC) or dysplasia following endoscopic resection (ER) for early gastric cancer (EGC) or dysplasia. Methods: PubMed, Cochrane Library, MEDLINE, and EMBASE were searched until 31 October 2023, and randomized controlled trials or cohort studies were peer-reviewed. The incidence of metachronous gastric lesions (MGLs) including MGC or dysplasia was compared between Helicobacter pylori persistent and negative groups, eradicated and negative groups, and eradicated and persistent groups. Results: Totally, 21 eligible studies including 82,256 observations were analyzed. Compared to those never infected, Helicobacter pylori persistent group (RR = 1.58, 95% CI = 0.98-2.53) trended to have a higher risk of MGLs and significantly in partial subgroups, while the post-ER eradicated group (RR = 0.79, 95% CI = 0.43-1.45) did not increase the risk of MGLs. Moreover, successful post-ER eradication could significantly decrease the risk of MGLs (RR = 0.54, 95% CI = 0.44-0.65) compared to those persistently infected. Sensitivity analysis obtained generally consistent results, and no significant publication bias was found. Conclusion: The persistent Helicobacter pylori infection trends to increase the post-ER incidence of MGC or dysplasia, but post-ER eradication can decrease the risk correspondingly. Post-ER screening and eradication of Helicobacter pylori have preventive effectiveness on MGC, and the protocol should be recommended to all the post-ER patients.Systematic review registration: The PROSPERO registration identification was CRD42024512101.

Clinicopathological features of hepatoid adenocarcinoma and non-hepatoid adenocarcinoma of the stomach: A systematic review and meta-analysis.

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is an extremely rare and unique malignant gastric tumor with a significantly worse prognosis than non-hepatoid adenocarcinoma of the stomach (non-HAS). The present study explored the clinicopathological features of HAS and non-HAS patients to provide insights into HAS treatment strategies. METHODS: From December 26, 2023, we performed a comprehensive search of the PubMed, Web of Science, Cochrane Library, and Embase.com databases for relevant studies. Two authors independently screened the studies, evaluated their quality, extracted data, and performed the analyses. This study was registered with PROSPERO on January 2, 2024. RESULTS: Nine retrospective studies were included for analysis after screening 833 articles. A total of 350 and 924 patients were enrolled in the HAS and non-HAS groups, respectively. While no significant differences were observed in age, sex, tumor size, T3 or T4 stage, and N2 or N3 stage between the two groups, the HAS group exhibited higher rates of lymph node metastasis (OR = 1.93, 95% CI: 1.19-3.13, p = 0.007), liver metastasis (OR = 3.45, 95% CI: 2.26-5.28, p < 0.001), and vascular invasion (OR = 2.76, 95% CI: 2.05-3.71, p < 0.001). Additionally, the HAS group had lower 3-year survival rates (HR = 2.35, 95% CI: 1.70-3.25, p < 0.001) and 5-year survival rates (HR = 3.63, 95% CI: 1.49-8.88, p = 0.005), but lower rates of lymphatic permeation (OR = 0.68, 95% CI: 0.47-0.99, p = 0.040). CONCLUSION: Based on the current clinical evidence, patients with HAS present distinct clinicopathological features, greater invasiveness, and poorer prognosis than non-HAS patients. Further research is warranted to develop optimal treatment strategies for HAS.

Distinct oral-associated gastric microbiota and Helicobacter pylori communities for spatial microbial heterogeneity in gastric cancer.

The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs. IMPORTANCE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

Development and validation of a nomogram for Siewert II esophagogastric junction adenocarcinoma: a retrospective analysis.

Background: Due to the complex histological type and anatomical structures, there has been considerable debate on the classification of adenocarcinoma of the esophagogastric junction (AEG), especially Siewert II AEG. Furthermore, neither the American Joint Committee on Cancer (AJCC) 7th tumor-node-metastasis (TNM) [esophageal adenocarcinoma (E) or gastric cancer (G)] nor the AJCC 8th TNM (E or G) accurately predicted the prognosis of patients with Siewert II AEG. Objective: This study aimed to investigate the factors influencing the survival and prognosis of patients with Siewert II AEG and establish a new and better prognostic predictive model. Design: A retrospective study. Methods: Patients with Siewert II AEG, retrieved from the Surveillance, Epidemiology, and End Results (SEER) databases, were assigned to the training set. Patients retrieved from a single tertiary medical center were assigned to the external validation set. Significant variables were selected using univariate and multivariate Cox regression analyses to construct the nomogram. Nomogram models were assessed using the concordance index (C-index), a calibration plot, decision curve analysis (DCA), and external validation. Results: Age, tumor grade, and size, as well as the T, N, and M stages, were included in the nomograms. For the SEER training set, the C-index of the nomogram was 0.683 (0.665-0.701). The C-index of the nomogram for the external validation set was 0.690 (0.653-0.727). The calibration curve showed good agreement between the nomogram estimations and actual observations in both the training and external validation sets. The DCA showed that the nomogram was clinically useful. Conclusion: The new predictive model showed significant accuracy in predicting the prognosis of Siewert II AEG.

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.

Incidence of cancer for patients after bariatric surgery: evidence from 33 cohort studies.

BACKGROUND: With the rising prevalence of severe obesity, bariatric surgery has emerged as a crucial treatment option. As the number of surgeries performed worldwide increases, there has been growing interest in the impact of bariatric surgery on cancer incidence. While several studies have examined this relationship, the topic remains controversial. OBJECTIVES: We conducted this systematic review of cohort studies with meta-analysis to evaluate the effect of bariatric surgery versus nonsurgical treatment on overall cancer incidence. However, the effects may vary when focusing on specific cancer types, surgical procedures, or gender, so we conducted additional subgroup analyses. SETTING: A meta-analysis. University hospital. METHODS: The Cochrane, Embase, PubMed, and Web of Science databases were searched for studies from 1 January 2000 to 1 December 2022. Meta-analysis was conducted to evaluate the pooled effect and further implemented subgroup analysis stratified by cancer type, operation type, and sex. RESULTS: All cohort studies were included in this meta-analysis from 18,216 studies. The overall cancer incidence demonstrated a significant decrease in the group with bariatric surgery (odds ratios [OR] = .56, P = .000, 95% CI .46 to .68). In subgroup analysis, similar decrease effect was found in 9 cancers. Furthermore, the incidence of cancer decreased significantly in male (OR = .66, P = .001, 95% CI .51 to .85) and female patients (OR = .63, P = .000, 95% CI .57 to .69) and patients undergoing gastric bypass (OR = .46, P = .000, 95% CI .33 to .63) or sleeve gastrectomy (OR = .44, P = .001, 95% CI .27 to .70). CONCLUSIONS: In the overall analysis, bariatric surgery could reduce the incidence of cancer significantly. Further large-scale well-matched studies are needed to verify the protective effect of bariatric surgery on cancer incidence.

Helicobacter pylori infection prevalence declined among an urban health check-up population in Chengdu, China: a longitudinal analysis of multiple cross-sectional studies.

Objectives: The efficacy of updated health policy in improving the generalization of Helicobacter pylori screening and eradication in southwest China was assessed in a longitudinal analysis of multiple cross-sectional studies from an institution. Methods: In the periods 2009-2010, 2013-2014, and 2019-2021, 8,365, 16,914, and 18,281 urban observations from health check-ups at West China Hospital were analyzed, respectively. The 14C-urea or 13C-urea breath test was consistently used for H. pylori detection. The protocol has been reported elsewhere (PROSPERO Registration number: CRD42019120764). Results: The overall prevalence of H. pylori dramatically decreased from 53.1% to 30.7% over the past decade (OR = 0.39, 95% CI 0.37-0.41), with a similar decline in all sex-specific and age-specific subgroups. The age-specific prevalence consistently increased before 40 years of age and always peaked at 50-59 years. Longitudinal clearance increased along with aging, and prevalence dropped to 22.6%, 25.1%, and 23.6% in the 40-49, 50-59, and 60-69 years initial age groups, respectively. Conclusion: The generalization of H. pylori screening and eradication could greatly contribute to the control of H. pylori infection among urban health check-up populations and lower gastric cancer incidence.

Optimal timing of surgery for gastric cancer after neoadjuvant chemotherapy: a systematic review and meta-analysis.

BACKGROUND: Following neoadjuvant chemotherapy, surgical resection is one of the most preferred treatment options for locally advanced gastric cancer patients. However, the optimal time interval between chemotherapy and surgery is unclear. This review aimed to identify the optimal time interval between neoadjuvant chemotherapy and surgery for advanced gastric cancer. METHODS: Beginning on November 12, 2022, we searched the PubMed, Cochrane Library, Web of Science databases, and Embase.com databases for relevant English-language research. Two authors independently screened the studies, assessed their quality, extracted the data, and analyzed the results. The primary goal was to investigate the relationship between the time interval to surgery (TTS) and long-term survival outcomes for patients. This study has been registered with PROSPERO (CRD42022365196). RESULTS: After an initial search of 4880 articles, the meta-analysis review ultimately included only five retrospective studies. Ultimately, this meta-analysis included 1171 patients, of which 411 patients had TTS of < 4 weeks, 507 patients had TTS of 4-6 weeks, and 253 patients had TTS of > 6 weeks. In survival analysis, patients with TTS of > 6 weeks had poorer overall survival outcomes than patients with TTS of 4-6 weeks (HR = 1.34, 95% CI: 1.03-1.75, P = 0.03). No significant differences were found in terms of disease-free survival the groups. CONCLUSION: Based on the current clinical evidence, patients with locally advanced gastric cancer may benefit better with a TTS of 4-6 weeks; however, this option still needs additional study.

Association between circulating tumor cells in the peripheral blood and the prognosis of gastric cancer patients: a meta-analysis.

Background: Research on the correlation between circulating tumor cells (CTCs) and gastric cancer (GC) has increased rapidly in recent years. However, whether CTCs are associated with GC patient prognosis is highly controversial. Objective: This study aims to evaluate the value of CTCs to predict the prognosis of GC patients. Design: A meta-analysis. Data Sources and Methods: We searched the PubMed, Embase, and Cochrane Library databases for studies that reported the prognostic value of CTCs in GC patients before October 2022. The association between CTCs and overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS) and progression-free survival (PFS) of GC patients was assessed. Subgroup analyses were stratified by sampling times (pre-treatment and post-treatment), detection targets, detection method, treatment method, tumor stage, region, and HR (Hazard Ratio) extraction methods. Sensitivity analysis was performed by removing individual studies to assess the stability of the results. Publication bias was evaluated using funnel plots, Egger's test, and Begg's test. Results: We initially screened 2000 studies, of which 28 were available for further analysis, involving 2383 GC patients. The pooled analysis concluded that the detection of CTCs was associated with poor OS (HR = 1.933, 95% CI 1.657-2.256, p < 0.001), DFS/RFS (HR = 3.228, 95% CI 2.475-4.211, p < 0.001), and PFS (HR = 3.272, 95% CI 1.970-5.435, p < 0.001). Furthermore, the subgroup analysis stratified by tumor stage (p < 0.01), HR extraction methods (p < 0.001), detection targets (p < 0.001), detection method (p < 0.001), sampling times (p < 0.001), and treatment method (p < 0.001) all showed that CTC detection was associated with poor OS and DFS/RFS for GC patients. Furthermore, the study showed that CTCs were associated with the poor DFS/RFS of GC when CTCs were detected for patients from Asian or No-Asian regions (p < 0.05). In addition, higher CTCs predicted poorer OS for GC patients who are from Asian regions (p < 0.001), but without statistical difference for GC patients from No-Asian regions (p = 0.490). Conclusion: CTC detection in peripheral blood was associated with poor OS, DFS/RFS, and PFS in patients with GC.

Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications.

In the past period, due to the rapid development of next-generation sequencing technology, accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response. More importantly, available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible. However, intricate complexities exist, and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment. The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development, and to highlight the relationship between gut microbes and the efficacy of immunotherapy, chemotherapy, radiation therapy and cancer surgery, which may provide insights into the formulation of individualized therapeutic strategies for cancer management. In addition, the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized. Although many challenges remain for now, the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies, and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.

Is No. 12a Lymph Node Dissection Compliance Necessary in Patients Who Undergo D2 Gastrectomy for Gastric Adenocarcinomas? A Population-Based Retrospective Propensity Score Matching Study.

LN dissection is essential for accurately staging and improving GC patient prognosis. However, the compliance rate for No. 12a LND in practice is low, and its necessity is controversial. Data from GC patients who underwent total gastrectomy (TG)/distal gastrectomy (DG) plus D2 lymphadenectomy between January 2000 and December 2017 at West China Hospital, Sichuan University were reviewed. No. 12a LND noncompliance's effect on the long-term prognosis of patients with GC after D2 gastrectomy was explored. Of the 2788 patients included, No. 12a LND noncompliance occurred in 1753 patients (62.9%). Among 1035 patients with assessable LNs from station 12a, 98 (9.5%) had positive LNs detected at station 12a. No. 12a LN metastasis patients (stage IV not included) had significantly better overall survival (OS) than TNM stage IV patients (p = 0.006). Patients with No. 12a LND compliance had a significantly higher OS than those without, both before (p < 0.001) and after (p < 0.001) PSM. Cox multivariate analysis confirmed that No. 12a LND noncompliance was an independent prognostic factor before (HR 1.323, 95% CI 1.171-1.496, p < 0.001) and after (HR 1.353, 95% CI 1.173-1.560, p < 0.001) PSM. In conclusion, noncompliance with No. 12a LND compromised the long-term survival of patients who underwent D2 gastrectomy for GC.

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 Gastrectomy for early-stage gastric cancer patients with or without preserving celiac branches of vagus nerves: A meta-analysis.

BACKGROUND: Vagus nerve-preserving gastrectomy is increasingly popular in treating gastric cancer in the early stage, however the long and short-term outcomes after gastrectomy while preserving the celiac branch of the vagus nerve are not well defined. We aimed to summarize and compare perioperative and longer-term outcomes after celiac branch vagus nerve-preserving gastrectomy (CBP, preserving both the celiac and hepatic branches of the vagus nerve), compared to those without CBP (non-CBP, only the hepatic branch of the vagus nerve is preserved). METHODS: We searched the Embase, PubMed, Cochrane Library and Web of Science databases for papers published before October 2021. The primary results were evaluated by short-term and long-term postoperative complications, whereas the secondary outcomes included surgery-related parameters, recovery-related parameters and overall survival. Random-effects or fixed-effects model were used to estimate odds ratio, and weighted mean difference for the outcomes. The underlying publication bias was identified via funnel charts, Begg's test and Egger's test. Sensitivity analysis was conducted by removing the research one by one. RESULTS: A total of 9 studies consisting of 8 retrospective studies and one randomized control trial were included. The analysis included 1,109 patients, with 568 (51.2%) of patients receiving CBP and 541 (48.8%) patients who received non-CBP. The CBP group had a shorter time in terms of first flatus (weighted mean difference = -0.436, 95% confidence interval: -0.603 to -0.269; P < 0.001) and hospital stay (weighted mean difference = -0.456, 95% confidence interval: -0.874 to -0.037, P = 0.033) than the non-CBP group, but the time to the start of oral intake was comparable between the groups. Regarding short-term complications and surgery-related parameters, between CBP and non-CBP, no evident differences were observed in pancreatic complications, anastomotic leakage, postoperative bleeding, operation time, blood loss or lymph nodes examined. In terms of long-term complications, the incidence of gallstones in CBP was lower than that in non-CBP (odds ratio = 0.582, 95% confidence interval: 0.356-0.953, P = 0.031), and the incidence of bile reflux in CBP was lower than that in non-CBP (odds ratio = 0.473, 95% confidence interval: 0.280-0.800, P = 0.005). However, the prevalence rates of diarrhea, early dumping syndrome, esophageal reflux, and delayed gastric emptying were comparable between CBP and non-CBP. CONCLUSION: The present research showed that gastric cancer patients in the early stage under CBP were superior to those without CBP in terms of incidence of gallstones, bile reflux, time of first flatus and hospital stay. Furthermore, it is imperative to conduct randomized control studies with larger sample sizes to determine the oncological survival outcomes when preserving the celiac branch.

Linear Stapler versus Circular Stapler for Patients Undergoing Anastomosis for Laparoscopic Gastric Surgery: A Meta-Analysis.

BACKGROUND: Anastomotic devices, including linear staplers (LSs) and circular staplers (CSs), have been widely used after laparoscopic gastric surgery. However, it is controversial whether linear stapling is superior to circular stapling for anastomosis. Thus, we conducted a meta-analysis to compare the aspects of postoperative complications, particularly anastomotic stricture and anastomotic leakage, on the use of the two techniques to assist clinical decision-making. METHODS: We conducted a systematic search using Embase, PubMed, and Cochrane Library to evaluate studies that compared LSs and CSs after laparoscopic gastric surgery. RESULTS: Pooled analysis suggested that patients who received LSs had fewer postoperative complications (P = 0.019), and anastomotic complications (P < 0.001), stricture (P = 0.001), and bleeding (P = 0.005). The subgroup analyses showed that LSs caused fewer anastomotic complications (P < 0.001), anastomotic strictures (P < 0.001), and postoperative hemorrhage (P = 0.007) in patients with gastric cancer than CS. In addition, LSs caused fewer incidences of overall morbidity (P = 0.042), anastomotic strictures (P = 0.023), postoperative hemorrhage (P < 0.001), wound infection (P < 0.001), and shorter length of hospital stay (P = 0.048) in patients with obesity. Furthermore, the subgroup analyses showed that the use of LS resulted in lower overall morbidity (P = 0.042), anastomotic stricture (P = 0.023), wound infection (P < 0.001), length of hospital stay (P = 0.048), and postoperative hemorrhage (P < 0.001) when applied in gastrojejunostomy, while LSs resulted in fewer anastomotic complications (P < 0.001), anastomotic stricture (P = 0.016) than CS when applied in esophagojejunostomy. CONCLUSION: Compared with CSs, LSs yielded a lower incidence of overall morbidity, anastomotic complications, anastomotic stricture, bleeding, and wound infection, indicating that linear stapling is safer and more efficient than circular stapling when performing anastomosis after laparoscopic gastric surgery.

Assessment of indocyanine green fluorescence lymphography on lymphadenectomy during minimally invasive gastric cancer surgery: a systematic review and meta-analysis.

BACKGROUND: In recent years, indocyanine green fluorescence lymphography has been introduced for lymphatic mapping in gastric cancer surgery. The aim of this study was to investigate the efficacy of ICGFL in lymph node dissection during minimally invasive surgery for gastric cancer. METHODS: A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed from the inception to January 2021 for all studies comparing ICGFL with non-ICGFL in GC patients undergoing minimal access gastrectomy. The primary outcome was the total number of harvested lymph nodes. The secondary endpoints were the number of metastatic LNs, operative time, estimated blood loss, and postoperative complications. The registration number of this protocol is PROSPERO CRD42020203443. RESULTS: A total of 13 studies including 1882 participants were included. In this meta-analysis, the use of ICGFL was associated with a higher number of harvested LNs (40.33 vs. 33.40; MD = 6.93; 95%CI: 4.28 to 9.58; P < 0.0001; I2 = 86%). No significant difference was found between the ICGFL and control groups in terms of metastatic LNs (2.63 vs. 2.42; MD = 0.21; 95%CI: -0.46 to 0.87; P = 0.54; I2 = 0%). In addition, the use of ICGFL could be safely performed without increasing the operative time (P = 0.49), estimated blood loss (P = 0.26) and postoperative complications (P = 0.54). CONCLUSION: The use of ICGFL may be a useful tool facilitating complete lymph node dissection during minimally invasive GC resection. However, more high-quality RCTs with large sample size are needed to validate this issue.

Deep learning-based AI model for signet-ring cell carcinoma diagnosis and chemotherapy response prediction in gastric cancer.

PURPOSE: We aimed to develop a noninvasive artificial intelligence (AI) model to diagnose signet-ring cell carcinoma (SRCC) of gastric cancer (GC) and identify patients with SRCC who could benefit from postoperative chemotherapy based on preoperative contrast-enhanced computed tomography (CT). METHODS: A total of 855 GC patients with 855 single GCs were included, of which 249 patients were diagnosed as SRCC by histopathologic examinations. The AI model was generated with clinical, handcrafted radiomic, and deep learning features. Model diagnostic performance was measured by area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, while predictive performance was measured by Kaplan-Meier curves. RESULTS: In the test cohort (n = 257), the AUC, sensitivity, and specificity of our AI model for diagnosing SRCC were 0.786 (95% CI: 0.721-0.845), 77.3%, and 69.2%, respectively. For the entire cohort, patients with AI-predicted high risk had a significantly shorter median OS compared with those with low risk (median overall survival [OS], 38.8 vs. 64.2 months, p = 0.009). Importantly, in pathologically confirmed advanced SRCC patients, AI-predicted high-risk status was indicative of a shorter overall survival (median overall survival [OS], 31.0 vs. 54.4 months, p = 0.036) and marked chemotherapy resistance, whereas AI-predicted low-risk status had substantial chemotherapy benefit (median OS [without vs. with chemotherapy], 26.0 vs. not reached, p = 0.013). CONCLUSIONS: The CT-based AI model demonstrated good performance for diagnosing SRCC, stratifying patient prognosis, and predicting chemotherapy responses. Advanced SRCC patients with AI-predicted low-risk status may benefit substantially from adjuvant chemotherapy.

The role and mechanism of claudins in cancer.

Claudins are a tetraspan membrane protein multigene family that plays a structural and functional role in constructing tight junctions. Claudins perform crucial roles in maintaining cell polarity in epithelial and endothelial cell sheets and controlling paracellular permeability. In the last two decades, increasing evidence indicates that claudin proteins play a major role in controlling paracellular permeability and signaling inside cells. Several types of claudins are dysregulated in various cancers. Depending on where the tumor originated, claudin overexpression or underexpression has been shown to regulate cell proliferation, cell growth, metabolism, metastasis and cell stemness. Epithelial-to-mesenchymal transition is one of the most important functions of claudin proteins in disease progression. However, the exact molecular mechanisms and signaling pathways that explain why claudin proteins are so important to tumorigenesis and progression have not been determined. In addition, claudins are currently being investigated as possible diagnostic and treatment targets. Here, we discuss how claudin-related signaling pathways affect tumorigenesis, tumor progression, and treatment sensitivity.