Background Recently, evidence has emerged that palliative gastrectomy in patients with stage IV gastric cancer may offer some survival benefits. However, the decision whether to perform primary tumor surgery remains challenging for surgeons, and investigations into models that are predictive of prognosis are scarce. Current study aimed to develop and validate prognostic nomograms for patients with metastatic gastric adenocarcinoma treated with palliative gastrectomy. Methods The development dataset comprised 1186 patients from the Surveillance, Epidemiology, and End Results Program who were diagnosed with metastatic gastric adenocarcinoma in 2004–2011, while the validation dataset included 407 patients diagnosed in 2012–2015. Variables were incorporated into a Cox proportional hazards model to identify independent risk factors for survival. Both pre- and postoperative nomograms for predicting 1- or 2-year survival probabilities were constructed using the development dataset. The concordance index (c-index) and calibration curves were plotted to determine the accuracy of the nomogram models. Finally, the cut-off value of the calculated total scores based on preoperative nomograms was set and validated by comparing survival with contemporary cases without primary tumor surgery. Results Age, tumor size, location, grade, T stage, N stage, metastatic site, scope of gastrectomy, number of examined lymph node(s), chemotherapy and radiotherapy were risk factors of survival and were included as variables in the postoperative nomogram; the c-indices of the development and validation datasets were 0.701 (95% confidence interval [CI]: 0.693–0.710) and 0.699 (95% CI: 0.682–0.716), respectively. The preoperative nomogram incorporated age, tumor size, location, grade, depth of invasion, regional lymph node(s) status, and metastatic site. The c-indices for the internal (bootstrap) and external validation sets were 0.629 (95% CI: 0.620–0.639) and 0.607 (95% CI: 0.588–0.626), respectively. Based on the preoperative nomogram, patients with preoperative total score > 28 showed no survival benefit with gastrectomy compared to no primary tumor surgery. Conclusions Our survival nomograms for patients with metastatic gastric adenocarcinoma undergoing palliative gastrectomy can assist surgeons in treatment decision-making and prognostication.
Background: This study aimed to investigate the effect of palliative gastrectomy on survival in stage IV gastric cancer. Methods: Patients diagnosed with stage IV gastric cancer between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival curves were estimated by the Kaplan-Meier method before and after propensity score matching (PSM). Univariate and multivariate Cox analyses were performed to evaluate risk factors for survival in patients who underwent palliative gastrectomy.Results: We examined 6,529 patients with stage IV gastric cancer, of which 625 underwent palliative gastrectomy. Using a 1:2 PSM, the 625 patients were matched with 1,250 patients from the no gastrectomy group. The overall survival was higher in the gastrectomy group before [hazard ratio (HR) =0.57, 95% confidence interval (CI): 0.53-0.62, P<0.0001] and after PSM (HR =0.51, 95% CI: 0.46-0.57, P<0.0001).Multivariate Cox analysis confirmed the survival benefits of palliative gastrectomy and chemotherapy. Older age, over-lapping lesions, non-adenocarcinomas, higher tumor grade, and lung metastasis significantly increased the risk of mortality. In the gastrectomy group, patients aged ≥80 years, diagnosed with grades 3/4 non-adenocarcinomas, or with lung metastasis showed poorer prognosis. However, chemotherapy could improve the survival of these patients. Conclusions:Palliative gastrectomy provides survival benefits to stage IV gastric cancer patients. However, age, tumor grade, tumor histology, and lung metastasis status should be considered while making a decision regarding gastrectomy. Chemotherapy should also be recommended for these patients.
Recent investigations have demonstrated that the chronic stress-induced behavioral disorders can be ameliorated by probiotics including Clostridium butyricum (C. butyricum) via the gut-brain-axis. However, the molecular mechanisms underlying the beneficial effects of C. butyricum on brain remain largely unknown. Here, we investigated whether chronic foot shock stress (CFSS) paradigm used for a hypertensive animal model could induce mood disorders such as anxiety, depression and cognitive impairments. Then, we assessed the impact of C. butyricum RH2 on the behavior disorders and neurobiological alterations in the hippocampus. Male Sprague-Dawley (SD) rats received intermittent electric shocks for consecutive 14 days and were treated with C. butyricum RH2 for 17 days. Anxiety- or depression-like behaviors were evaluated by open field test (OFT), and elevated plus maze (EPM). The Morris water maze test (MWM) was used to evaluate the cognitive functions. CFSS intervention led to mild anxiety- or depression-like behavior or cognitive impairment and C. butyricum RH2 treatment reversed the CFSS-induced symptoms. The serum ACTH or CORT was increased following CFSS but was completely reversed by C. butyricum RH2 treatment. In the hippocampus of CFSS rats, the expressions of BDNF and TrkB were downregulated but proBDNF and P75NTR were upregulated. These expression changes were partially reversed by C. butyricum RH2, suggesting a mode of action on BDNF and proBDNF balance. CFSS exposure resulted in downregulation of tissue-type plasminogen activator (tPA) but upregulation of plasminogen activator inhibitor 1(PAI-1), which could contribute to the decrease in BDNF by reduced conversion from proBDNF to BDNF in the hippocampus. C. butyricum RH2 treatment reversed the upregulated PAI-1 but not the downregulated tPA, which was in parallel with the amelioration of behavioral abnormalities, suggesting a novel tPA independent mechanism for PAI-1 action. Our results demonstrate for the first time that C. butyricum RH2 attenuates stress-induced behavior disorders via inhibiting the expression of brain PAI-1.
The global incidence of inflammatory bowel disease (IBD) has increased rapidly in recent years, but its exact etiology remains unclear. In the past decade, IBD has been reported to be associated with dysbiosis of gut microbiota. Although not yet proven to be a cause or consequence of IBD, the common hypothesis is that at least some alterations in the microbiome are protective or pathogenic. Furthermore, intestinal epithelial cells (IECs) serve as a protective physical barrier for gut microbiota, essential for maintaining intestinal homeostasis and actively contributes to the mucosal immune system. Thus, dysregulation within the intestinal epithelium increases intestinal permeability, promotes the entry of bacteria, toxins, and macromolecules, and disrupts intestinal immune homeostasis, all of which are associated with the clinical course of IBD. This article presents a selective overview of recent studies on bacterial mechanisms that may be protective or promotive of IBD in biological models. Moreover, we summarize and discuss the recent discovery of key modulators and signaling pathways in the IECs that could serve as potential IBD therapeutic targets. Understanding the role of the IECs in the pathogenesis of IBD may help improve the understanding of the inflammatory process and the identification of potential therapeutic targets to help ameliorate this increasingly common disease.
BackgroundTo evaluate whether the addition of taxane to platinum and fluoropyrimidines in adjuvant chemotherapy would result in longer survival than platinum plus fluoropyrimidines in patients who underwent curative gastrectomy.MethodsThis study retrospectively analyzed survival for patients with stage Ⅱ-Ⅲ gastric adenocarcinoma who received curative gastrectomy and adjuvant chemotherapy with platinum plus fluoropyrimidines (PF group) or taxanes and platinum plus fluoropyrimidines (TPF group). Survival curves were estimated using the Kaplan-Meier method, and the differences were compared using the log-rank test.ResultsBaseline characteristics were balanced between the PF group and TPF group. The median disease-free survival (DFS) was 14.9 months (95% CI: 11.0-18.8) in the PF group and 13.8 months (95% CI: 9.3-18.3) in the TPF group (HR=0.90, 95% CI: 0.63-1.29, log-rank test, P=0.560). The median overall survival (OS) was 30.0 months for patients in the PF group (95% CI: 24.5-35.5) and 25.6 months (95% CI: 22.3-28.9) for those in the TPF group (HR=0.93, 95% CI: 0.64-1.35, log-rank test, P=0.705).ConclusionFor stage Ⅱ-Ⅲ gastric adenocarcinoma, the adjuvant triple combination of TPF regimen after curative gastrectomy did not demonstrate survival benefit compared to the PF regimen.
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