What is the impact of microbiota on dry eye: a literature review of the gut-eye axis.

BACKGROUND: Dry eye is a chronic and multifactorial ocular surface disease caused by tear film instability or imbalance in the microenvironment of the ocular surface. It can lead to various discomforts such as inflammation of the ocular surface and visual issues. However, the mechanism of dry eye is not clear, which results in dry eye being only relieved but not cured in clinical practice. Finding multiple environmental pathways for dry eye and exploring the pathogenesis of dry eye have become the focus of research. Studies have found that changes in microbiota may be related to the occurrence and development of dry eye disease. METHODS: Entered the keywords "Dry eye", "Microbiota", "Bacteria" through PUBMED, summarised the articles that meet the inclusion criteria and then filtered them while the publication time range of the literature was defined in the past 5 years, with a deadline of 2023.A total of 13 clinical and 1 animal-related research articles were screened out and included in the summary. RESULTS: Study found that different components of bacteria can induce ocular immune responses through different receptors present on the ocular surface, thereby leading to an imbalance in the ocular surface microenvironment. Changes in the ocular surface microbiota and gut microbiota were also found when dry eye syndrome occurs, including changes in diversity, an increase in pro-inflammatory bacteria, and a decrease in short-chain fatty acid-related bacterial genera that produce anti-inflammatory effects. Fecal microbiota transplantation or probiotic intervention can alleviate signs of inflammation on the ocular surface of dry eye animal models. CONCLUSIONS: By summarizing the changes in the ocular surface and intestinal microbiota when dry eye occurs, it is speculated and concluded that the intestine may affect the occurrence of eye diseases such as dry eye through several pathways and mechanisms, such as the occurrence of abnormal immune responses, microbiota metabolites- intervention of short-chain fatty acids, imbalance of pro-inflammatory and anti-inflammatory factors, and release of neurotransmitters, etc. Analyzing the correlation between the intestinal tract and the eyes from the perspective of microbiota can provide a theoretical basis and a new idea for relieving dry eyes in multiple ways in the future.

Clinical significance of tumor deposits in gastric cancer after radical gastrectomy: a propensity score matching study.

OBJECTIVE: The value of tumor deposits (TDs) in the prognosis and staging of gastric cancer (GC) is still under debate. This study aims to evaluate the prognostic value of TDs and the best ways to incorporate TDs in the TNM classification of GC. METHODS: Patients (n = 3460) undergoing curative gastrectomy for GC in the West China Hospital from 2005 to 2017 were retrospectively reviewed and divided into two groups according to the TD status (positive vs. negative). Later, clinicopathological features and overall survival (OS) between the two groups were compared. Thereafter, the associations between the presence of TD and other clinicopathological factors were evaluated through logistic regression. In addition, univariate and multivariate Cox regression were conducted for determining prognostic factors. The possibility of selection bias was reduced through conducting the 1:1 propensity score matching (PSM) analysis. The modified classification systems proposed previously that incorporated TDs into the TNM staging system were assessed. RESULTS: There were 10.5% of patients (362/3460) diagnosed with TDs. TDs were significantly related to unfavorable factors such as advanced T stage and N stage and independently associated with poor prognosis. The 5-year OS of patients with TDs was significantly lower than that of patients without TDs (31.0% vs. 60.9%, P < 0.001), whereas higher than that of patients with peritoneal metastasis (31.0% vs. 5.0%, P < 0.001). In patients receiving chemotherapy, the 5-year OS of patients with TDs was also significantly lower than that of patients without TDs (42.0% vs. 50.9%, P = 0.026). Moreover, the system incorporating TDs in the TNM classification as metastatic lymph nodes outperformed others. CONCLUSIONS: TDs are related to the aggressive characteristics and are an independent prognostic factor for GC. Incorporating TDs in the TNM classification as the metastatic lymph nodes increases the accuracy in predicting prognosis.

Indocyanine green fluorescence angiography prevents anastomotic leakage in rectal cancer surgery: a systematic review and meta-analysis.

BACKGROUND: The role of intraoperative use of indocyanine green (ICG) fluorescence angiography (ICGFA) to prevent anastomotic leakage (AL) in rectal cancer surgery remains controversial. METHODS: The systematic review for studies evaluating ICGFA in patients undergoing rectal cancer surgery in PubMed, Embase, Web of Science, and the Cochrane Library was performed up to April 30, 2020. The primary outcome was the incidence of AL. The analysis was performed using RevMan v5.3 and Stata v12.0 software. RESULTS: Eighteen studies comprising 4038 patients were included. In the present meta-analysis, intraoperative use of ICGFA markedly reduced AL rate (OR = 0.33; 95% CI: 0.24-0.45; P < 0.0001; I2 = 0%) in rectal cancer surgery, which was still significant in surgeries limited to symptomatic AL (OR = 0.44; 95% CI: 0.31-0.64; P < 0.0001; I2 = 22%). This intervention was also associated with shorter postoperative stays (MD = - 1.27; 95% CI: - 2.42 to - 0.13; P = 0.04; I2 = 60%). However, reoperation rate (OR = 0.61; 95% CI: 0.34-1.10; P = 0.10; I2 = 6%), ileus rate (OR = 1.30; 95% CI: 0.60-2.82; P = 0.51; I2 = 56%), and surgical site infection rate (OR = 1.40; 95% CI: 0.62-3.20; P = 0.42; I2 = 0%) were not significantly different between the two groups. CONCLUSION: The use of ICGFA was associated with a lower AL rate after rectal cancer resection. However, more multi-center RCTs with large sample size are required to further verify the value of ICGFA in rectal cancer surgery.

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

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

Prognostic impact of Borrmann classification on advanced gastric cancer: a retrospective cohort from a single institution in western China.

BACKGROUND: Due to the controversy over the prognostic significance of Borrmann type in patients with gastric cancer (GC), the present study was to investigate the clinical value of Borrmann type in advanced GC. METHODS: We retrospectively evaluated 2092 patients with advanced GC and subsequently examined the clinicopathological characteristics and prognosis of patients stratified by Borrmann type. RESULTS: Patients were divided into three groups according to Borrmann type (Borrmann types I+II, III, and IV). Patients with Borrmann types III and IV had larger size, more poorly differentiated tumor type, more advanced tumor stage, and higher chance of involving the entire stomach. The overall survival (OS) rates were significantly different among the three groups (p < 0.001). Stratification analysis revealed significant OS rates among the three groups in tumor-node-metastasis (TNM) stage III (p < 0.001) and TNM stage IV (p = 0.008). Multivariate analysis revealed that Borrmann types, adjuvant chemotherapy, curative resection, and TNM stage were all independent predictors of OS among GC patients. The subgroup analysis indicated that Borrmann type was an independent predictor of OS among GC patients who undergone curative resection and with TNM stage III cancer. However, curative resection and postoperative chemotherapy failed to prolong the survival of patients with Borrmann type IV. CONCLUSIONS: The clinicopathological characteristics and prognosis of patients with three Borrmann types of GC were different. Borrmann type can be simply used as a valuable factor to predict survival in advanced GC patients, especially in those TNM stage III undergoing curative resection. Additionally, more attention should be paid to the treatment for Borrmann type IV GC.

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

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

Characteristics and survival outcomes related to the infra-pyloric lymph node status of gastric cancer patients.

BACKGROUND: To study metastasis to the infra-pyloric (no. 6) lymph nodes and their subgroups and the related risk factors of gastric cancer patients. METHODS: Gastric cancer patients who underwent gastrectomy with complete postoperative pathological information on the no. 6 lymph node station and its subgroups from January 1, 2008, to December 31, 2011, were included. The clinicopathological characteristics and survival outcomes were analyzed. RESULTS: A total of 121 patients were included; they had 6.1 ± 7.7 positive lymph nodes, and 35.1 ± 14.2 lymph nodes were examined. The overall lymph node positivity rate was 67.8% (82/121) with a positivity rate of 28.1% (34/121) for the no. 6 lymph nodes. The metastasis rate was 6.6% for the no. 6a nodes, 6.6% for the no. 6b nodes, and 21.5% for the no. 6c nodes. Also, no. 8a (OR = 1.329, p = 0.017) and no. 9 (OR = 1.250, p = 0.022) nodal positivity and lower third tumor location (OR = 1.278, p = 0.001) were independent risk factors for no. 6 lymph nodal metastasis. There was a significant survival difference between patients with positive and negative no. 6 lymph nodes and patients with metastasis to other lymph node stations (p <  0.001). CONCLUSIONS: Patients with no. 6 lymph node metastasis have poor survival outcomes. Complete infra-pyloric lymphadenectomy is necessary and crucial for gastric cancer patients.

Nanomedicine Combats Drug Resistance in Lung Cancer.

Lung cancer is the second most prevalent cancer and the leading cause of cancer-related death worldwide. Surgery, chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy are currently available as treatment methods. However, drug resistance is a significant factor in the failure of lung cancer treatments. Novel therapeutics have been exploited to address complicated resistance mechanisms of lung cancer and the advancement of nanomedicine is extremely promising in terms of overcoming drug resistance. Nanomedicine equipped with multifunctional and tunable physiochemical properties in alignment with tumor genetic profiles can achieve precise, safe, and effective treatment while minimizing or eradicating drug resistance in cancer. Here, this work reviews the discovered resistance mechanisms for lung cancer chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy, and outlines novel strategies for the development of nanomedicine against drug resistance. This work focuses on engineering design, customized delivery, current challenges, and clinical translation of nanomedicine in the application of resistant lung cancer.

Enzyme-Responsive Branched Glycopolymer-Based Nanoassembly for Co-Delivery of Paclitaxel and Akt Inhibitor toward Synergistic Therapy of Gastric Cancer.

Combined chemotherapy and targeted therapy holds immense potential in the management of advanced gastric cancer (GC). GC tissues exhibit an elevated expression level of protein kinase B (AKT), which contributes to disease progression and poor chemotherapeutic responsiveness. Inhibition of AKT expression through an AKT inhibitor, capivasertib (CAP), to enhance cytotoxicity of paclitaxel (PTX) toward GC cells is demonstrated in this study. A cathepsin B-responsive polymeric nanoparticle prodrug system is employed for co-delivery of PTX and CAP, resulting in a polymeric nano-drug BPGP@CAP. The release of PTX and CAP is triggered in an environment with overexpressed cathepsin B upon lysosomal uptake of BPGP@CAP. A synergistic therapeutic effect of PTX and CAP on killing GC cells is confirmed by in vitro and in vivo experiments. Mechanistic investigations suggested that CAP may inhibit AKT expression, leading to suppression of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Encouragingly, CAP can synergize with PTX to exert potent antitumor effects against GC after they are co-delivered via a polymeric drug delivery system, and this delivery system helped reduce their toxic side effects, which provides an effective therapeutic strategy for treating GC.

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.

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.

Targeting drug-tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells.

Drug resistance remains the greatest challenge in improving outcomes for cancer patients who receive chemotherapy and targeted therapy. Surmounting evidence suggests that a subpopulation of cancer cells could escape intense selective drug treatment by entering a drug-tolerant state without genetic variations. These drug-tolerant cells (DTCs) are characterized with a slow proliferation rate and a reversible phenotype. They reside in the tumor region and may serve as a reservoir for resistant phenotypes. The survival of DTCs is regulated by epigenetic modifications, transcriptional regulation, mRNA translation remodeling, metabolic changes, antiapoptosis, interactions with the tumor microenvironment, and activation of signaling pathways. Thus, targeting the regulators of DTCs opens a new avenue for the treatment of therapy-resistant tumors. In this review, we first provide an overview of common characteristics of DTCs and the regulating networks in DTCs development. We also discuss the potential therapeutic opportunities to target DTCs. Last, we discuss the current challenges and prospects of the DTC-targeting approach to overcome acquired drug resistance. Reviewing the latest developments in DTC research could be essential in discovering of methods to eliminate DTCs, which may represent a novel therapeutic strategy for preventing drug resistance in the future.

Dissecting the genetic and microenvironmental factors of gastric tumorigenesis in mice.

Gastric cancer (GC) is one of the most frequent and lethal malignancies in the world. However, our understanding of the mechanisms underlying its initiation and progression is limited. Here, we generate a series of primary GC models in mice with genome-edited gastric organoids, which elucidate the genetic drivers for sequential transformation from dysplasia to well-differentiated and poorly differentiated GC. Further, we find that the orthotopic GC, but not the subcutaneous GC even with the same genetic drivers, display remote metastasis, suggesting critical roles of the microenvironment in GC metastasis. Through single-cell RNA-seq analyses and functional studies, we show that the interaction between fibronectin 1 on stomach-specific macrophages and integrin a6ß4 on GC cells promotes remote metastases. Taken together, our studies propose a strategy to model GC and dissect the genetic and microenvironmental factors driving the full-range gastric tumorigenesis.

Peritoneal Metastatic Cancer Stem Cells of Gastric Cancer with Partial Mesenchymal-Epithelial Transition and Enhanced Invasiveness in an Intraperitoneal Transplantation Model.

OBJECTIVES: This preliminary study is aimed at enriching and isolating peritoneal metastatic cancer stem cells (pMCSCs) of gastric cancer and assessing their epithelial-mesenchymal transition (EMT) phenotype and invasiveness. METHODS: Cancer stem cells of human gastric cancer (CSC-hGC) were previously isolated and transfected with green fluorescent protein and luciferase genes to validate the mouse model of peritoneal metastasis established via transplantation. The first and second generations ([G1] and [G2], respectively) of pMCSCs were isolated from intraperitoneally transplanted CSC-hGC (pMCSC-tGC) by spherical culture. CSC and EMT-related markers and regulators in the two generations of intraperitoneally transplanted tumors were examined by immunohistochemistry, immunofluorescence staining, and quantitative PCR. Cell mobility was examined by a transwell assay. RESULTS: The nude mouse model of intraperitoneally transplanted CSC-hGC was successful in establishing sequential formation of peritoneal tumors and enrichment of pMCSCs. CD44 and CD54 were consistently expressed in the two generations of transplanted tumors. In vitro cell (migration) assays and immunocytofluorescence assays showed that in pMCSC-tGC[G2], E-cad, Survivin, and Vimentin expression was stable; α-SMA expression was decreased; and OVOL2, GRHL2, and ZEB1 expression was increased. PCR analysis indicated that in pMCSC-tGC[G2], the mRNA expression of E-cad, α-SMA, MMP9, MMP2, and Vimentin was downregulated, while that of ZEB1, OVOL2, and GRHL2 was upregulated. In vivo tumor (homing) assays and immunohistochemical assays demonstrated that in pMCSC-tGC[G2], E-cad and Snail were upregulated, while α-SMA was downregulated. The numbers of migrated and invaded pMCSC-tGC[G1] and pMCSC-tGC[G2] were significantly higher than those of CSC-hGC in migration and invasion assays. CONCLUSIONS: pMCSCs might be a specific subpopulation that can be sequentially enriched by intraperitoneal transplantation. pMCSCs exhibited a tendency towards partial mesenchymal-epithelial transition, enhancing their invasiveness during homing and the formation of peritoneal tumors. However, these preliminary findings require validation in further experiments.

Prognostic Value of Changes in Preoperative and Postoperative Serum CA19-9 Levels in Gastric Cancer.

Objective: The prognostic significance of serum CA19-9 levels in gastric cancer patients remains a matter debate. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative serum CA19-9 levels in patients with gastric cancer. Methods: A total of 1,046 gastric cancer patients who underwent curative gastrectomy in West China Hospital of Sichuan University from January 2011 to December 2016 were analyzed retrospectively. Patients were categorized by minimum P-value using X-tile, while the baseline confounders for CA19-9 changes were balanced through propensity score matching (PSM). The relationships between CA19-9 changes and other clinicopathologic features were measured. Univariate and multivariate analysis were performed to explore the risk factors associated with survival outcomes. Results: We included 653 patients. Changes in CA19-9 levels significantly correlated with age, tumor size, macroscopic type, histological grade, T stage and TNM stage. Kaplan-Meier curves revealed that patients with CA19-9 changes <20% had significant better overall survival than those with changes more than 20% (p < 0.001); Cox regression analysis revealed the CA19-9 change (p = 0.010), gender (p = 0.031), histological grade (p = 0.036) and TNM stage (p < 0.001) were independent risk factors for survival after PSM. Stratification analysis indicated that patients with CA19-9 change more than 20% had worse prognosis that those with CA19-9 change no more than 20% in male (p = 0.002), poorly differentiated or undifferentiated type (p = 0.031) and TNM stage III (p = 0.006). Conclusion: Changes in preoperative and postoperative serum CA19-9 levels were closely associated with clinicopathological traits and was an independent prognostic factor in gastric cancer patients. This parameter may be a reliable marker for prediction of survival.

Clinicopathological characteristics and prognostic factors of remnant gastric cancer: A single-center retrospective analysis of 90 patients.

BACKGROUND: The prognosis of remnant gastric cancer (RGC) is significantly poor. However, the mechanism and some clinical features of RGC have not been fully understood and are still under debate. MATERIALS AND METHODS: From January 2000 to January 2014, 90 RGC patients were enrolled in this retrospective study. Patients were divided into two groups according to primary disease. Clinicopathological features and survival outcomes were compared between two groups. RESULTS: A total of 34 (37.8%) patients were diagnosed with remnant gastric cancer following benign disease (RGCB) and 56 (62.2%) were diagnosed with remnant gastric cancer following malignant disease (RGCM). The mean time interval from the primary operation to the development of RGC was 12.5 ±â€¯13.3 years in all RGC patients. The mean time interval in RGCB was significantly longer than that in RGCM (P < 0.01). The 1-, 2-, and 3- year overall survival rates of all patients were 56.1%, 38.2% and 33.2%, respectively. Univariate analysis indicated that tumor size, curability, histology type, serosa invasion, nodal involvement and distant metastasis were prognostic factors for RGC. The multivariate Cox regression analysis revealed that distant metastasis was an independent prognostic factor for RGC. CONCLUSION: RGC occurred earlier in patients with gastrectomy for primary malignant disease than for primary benign disease, even though the primary disease made no difference to the survival of RGC. Nonetheless, RGC patients experienced dismal overall survival. Therefore, early diagnosis plays a significant role in successfully carrying out curative resection and improving the prognosis for RGC.

Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer.

Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however, with no systematical investigation for prognostic genomic features. Here we report a systematic investigation conducted in 1868 Chinese gastric cancer patients indicating that signet-ring cells content was related to multiple clinical characteristics and treatment outcomes. We thus perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation, prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet-ring cell content, age at diagnosis, female/male ratio, and TNM stage. Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes, and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26 introduced cell lines. Overall, this study provides insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.

A Bottleneck in Understanding Metastatic Cancer Stem Cell of Peritoneal Seeding from Gastric Cancer: A Null Result in Brief.

The capture of peritoneal metastatic cancer stem cell of human gastric cancer (pMCSC-hGC) is important to further understand the mechanism of peritoneal metastasis in gastric cancer patients. Previously, cancer stem cells (CSCs) of gastric and rectal cancers were captured and identified. However, the bottleneck of capturing pMCSC-hGC may be the scarce surgical specimen and limited volume of peritoneal metastatic lesions from gastric cancer. Only 5.2% of patients were diagnosed of unpredictive peritoneal seeding intraoperatively, while none cell sphere were successfully formed through the identical culture approach based on peritoneal metastatic nodules. The attempt to enrich and capture pMCSC of transplanted gastric cancer (pMCSC-tGC) in immunodeficiency mice model through intraperitoneal injection of CSC-hGC may be a considerable and feasible alteration.

[Application of multimodal analgesia in radical gastrectomy for gastric cancer patients: a prospective nonrandomized controlled study].

OBJECTIVE: To compare the postoperative analgesia efficacy, rehabilitation parameters and complication between multimodal analgesia and traditional analgesia after radical gastrectomy for gastric cancer patients. METHODS: Patients with gastric cancer who underwent surgery in our hospital from October 2016 to December 2016 were enrolled in this prospective study. According to the non-randomized method, patients were assigned to multimodal analgesia group(n=32) and traditional analgesia group(n=33) in gastric cancer treatment team A and B in Department of Gastrointestinal Surgery, West China Hospital, Sichuan University. The treatment measures of group A were as follows: (1) The ratio of 1/1 diluted ropivacaine (100 mg, 10 ml) was infiltrated around the incision before abdomen closure, with incision sutured layer by layer. (2) Parecoxib sodium (40 mg) was injected intravenously every 12 hours after operation for 5 days. (3) Oxycodone-acetaminophen tablet was given orally on the first day or the second day after operation, 50 mg twice a day. (4) Patient-controlled analgesia was not used after operation. Patients in group B received direct suture of incision and patient-controlled analgesia. The pain score, postoperative rehabilitation and 30-day postoperative complications were collected and analyzed. RESULTS: Multimodal analgesia group had lower pain scores at 1 d (4.8±0.9), 2 d (4.3±1.0), 3 d (2.9±0.8), 4 d (2.4±0.7) and 5 d (1.7±0.7) after surgery, as compared to traditional analgesia group (5.9±0.9, P=0.000), (5.1±0.7, P=0.001), (3.9±0.8, P=0.000), (3.0±0.6, P=0.000), (2.6±0.7, P=0.000), with significant difference. Postoperative hospital stay [(8.2±1.6) days vs. (10.6±2.2) days, P=0.000], time to ambulation [(47.5±13.8) days vs. (66.2±16.8) days, P=0.000], time to first flatus [(76.4±25.2) days vs. (120.0±29.9) days, P=0.000], time to first defecate [(117.3±42.2) days vs. (159.7±30.7) days, P=0.000] and time to first fluid diet [(83.8±21.6) days vs. (141.9±33.9) days, P=0.000] in the multimodal analgesia group were significantly shorter than those in the traditional analgesia group. There was no significant difference between the two groups with respect to 30-day postoperative complication rate(9.4% vs. 9.1%, P=1.000). CONCLUSIONS: Multimodal analgesia can significantly reduce the postoperative pain and is beneficial to rehabilitation, meanwhile it does not increase the risk of postoperative complications. Multimodal analgesia is safe and effective for gastric cancer patients undergoing radical gastrectomy.

Learning curve for gastric cancer patients with laparoscopy-assisted distal gastrectomy: 6-year experience from a single institution in western China.

Laparoscopy-assisted distal gastrectomy (LADG) is widely used for gastric cancer (GC) patients nowadays. This study aimed to investigate the time trend of outcomes so as to describe the learning curve for GC patients with LADG at a single medical institution in western China over a 6-year period.A total of 246 consecutive GC patients with LADG were divided into 5 groups (group A: 46 patients from 2006 to 2007; group B: 47 patients in 2008; group C: 49 patients in 2009; group D: 73 patients in 2010; and group E: 31 patients in 2011). All surgeries were conducted by the same surgeon. Comparative analyses were successively performed by Mann-Whitney U test or Student t test among the 5 different groups for the clinical data, including clinicopathologic characteristics, surgical parameters, postoperative course, and survival outcomes, through which the learning curve was described.There were no differences in the baseline information among the 5 groups (P > 0.05), and the proportion of advanced GC patients with LADG slightly increased from 58.7% to 77.4% during the 6 years. Besides, the proportion of D2/D2+ lymphadenectomy and the number of retrieved lymph nodes gradually grew from 60.9% to 80.6% and from 20.0 to 28.8, respectively. In addition, the operation time decreased from 299.2 to 267.8 minutes, while the estimated blood loss dropped from 175.2 to 146.8 mL. Furthermore, some surgical parameters (surgical duration and blood loss) and postoperative course (such as postoperative complications, the time to ambulation, to first flatus, and to first liquid intake as well as the length of hospital stay) were all observed to be significantly different between group A and other groups (P < 0.05), illustrating a similar downward trend and remaining stable to form a plateau after 46 cases in group A. However, no difference on overall survival was found among these 5 groups, and multivariate analysis indicated that factors, such as age, tumor differentiation, tumor size, and T stage as well as N stage, were independent prognostic factors for patients with LADG.Improvement on surgical parameters and postoperative course can be seen over the past years, and the cutoff value of the learning curve of LADG for surgeons with rich experience in open operation might be 46 cases.