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Background Hepatocellular carcinoma (HCC), with Hepatitis B viurs X protein (HBx) as one of the main etiology, harbors various metabolic phenotypes for distinct nutrient availability inside solid tumors. Trichostatin A is a histone inhibitor, supposed to inhibit cancer development. However, the role of TSA in tumor cells with metabolic stress has received little investigation. Methods We built a HBx-overexpression hepatoma cell model with HBx plasmids transfection, and EBSS was applied in nutrient-deprived cell model. Through western blot, Q-PCR and immunoprecipitation, we further explored the molecular mechanism of TSA-related anti-cancer function. Results In our study here, we found that TSA inhibited HBx-enhanced metastasis in metabolic stress, and demonstrated that Sirtuin 3 (SIRT3), one of tumor suppressors in HCC, played a role in TSA-related anti-cancer function in metabolic stress, and TSA promoted SIRT3 transcription. Conclusions We suggest that TSA alleviated specific subset of HCC, the HBx-induced HCC in metabolic stress, through promoting SIRT3 transcription, suggesting that TSA is a potential drug for HCC treatment.

Background:There is controversy about the characteristics and prognostic implications of signet ring cell gastric cancers and non-signet ring cell gastric cancers.Objective:This study aims to evaluate clinicopathological characteristics and prognoses of signet ring cell carcinoma (SRCC) and non-signet ring cell carcinoma (NSRCC) of stomach.Methods:Studies compared between SRCC and NSRCC of the stomach after gastrectomy and published before September 1st, 2020, in the PubMed, Cochrane, and Embase databases, were identified systematically.Results:A total of 2,865 studies were screened, and 36 studies were included, with 19,174 patients in the SRCC group and 55,942 patients in the NSRCC group. SRCC patients were younger in age (P< 0.001), less likely to be male patients (P< 0.001), more afflicted with upper third lesions (P< 0.001), and presenting with more Borrmann type IV tumors (P= 0.005) than NSRCC patients. Lymph nodes metastasis was similar between SRCC and NSRCC patients with advanced tumor stage (OR: 0.86, 95% CI: 0.67–1.10,P= 0.23), but lower in the SRCC than NSRCC patients with early tumor stage (OR: 0.73; 95% CI: 0.56–0.98,P= 0.02). SRCC patients had comparable survival outcomes with NSRCC patients for early gastric cancers (HR: 1.05, 95% CI: 0.65–1.68,P< 0.001) but had significantly poor prognosis for patients with advanced tumor stage (HR: 1.50, 95% CI: 1.28–1.76,P< 0.001).Conclusions:Signet ring cell carcinomas of the stomach are an increasingly common histopathological subtype of gastric cancers. These kinds of patients tend to be younger in age and more often female. Although, signet ring cell gastric cancer is a negative prognostic factor for patients with advanced stage. The difference is that for early stage of signet ring cell gastric cancers, it has low lymph nodes metastasis rate and comparable prognosis with non-signet ring cell cancers.

Xiaonan Yin,1,* Yuan Yin,1,* Chaoyong Shen,1 Huijiao Chen,2 Jiang Wang,1 Zhaolun Cai,1 Zhixin Chen,1 Bo Zhang1 1Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; 2Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China *These authors contributed equally to this work Background: Regorafenib is a novel multikinase inhibitor (MKI) approved for use in the treatment of metastatic colorectal cancer (CRC), treatment-refractory gastrointestinal stromal tumors, and other solid tumor malignancies. However, the adverse events (AEs) associated with regorafenib have not been systematically investigated. Hence, we performed a meta-analysis to identify AEs associated with regorafenib in patients with advanced solid tumors.Methods: The databases of PubMed, MEDLINE, and Embase and abstracts presented in American Society of Clinical Oncology annual meetings were searched for relevant publications from January 2004 to September 2017. Eligible studies were limited to prospective randomized controlled trials (RCTs) that evaluate the use of regorafenib in patients with advanced solid tumors. Incidence, relative risk (RR), and 95% CIs were calculated using a random or fixed effects model on the basis of the heterogeneity of the included studies.Results: A total of 2,065 patients from six RCTs were included, and 1,340 of them received regorafenib and 725 received a placebo. Sixteen all-grade AEs and 15 high-grade AEs were investigated for their association with regorafenib. Results showed that hand–foot skin reaction (HFSR; 54%), diarrhea (33%), fatigue (32%), hypertension (31%), oral mucositis (28%), and anorexia (23%) were the most frequent clinical AEs. The most common high-grade (grade, $3) AEs were HFSR (16%), hypertension (13%), fatigue (6%), increased aspartate aminotransferase (AST; 6%), and hypophosphatemia (6%). Pooled RR showed that the use of regorafenib was associated with an increased risk of developing AEs. Subgroup analysis based on the prior MKI treatment showed that prior MKI treatment was associated with an increased incidence of all-grade anorexia (P=0.03) and a reduced incidence of high-grade increased AST (P=0.04). However, subgroup analysis based on the tumor type showed that no significant differences were found when comparing the RR of all-grade and high-grade AEs in patients with CRC or non-CRC.Conclusion: The meta-analysis systematically investigated regorafenib-associated AEs. Knowledge of these AEs is essential for minimizing treatment-related toxicities and improving clinical outcomes. Keywords: regorafenib, adverse event, AE, safety, multikinase inhibitor, meta-analysis&nbsp

The efficacy of agents targeting epidermal growth factor receptor (EGFR) in patients with various cancers was well elucidated. However, the safety profile of EGFR tyrosine kinase inhibitors (EGFR‐TKIs) has not been systematically investigated. This meta‐analysis aimed to evaluate the safety profile of EGFR‐TKIs in patients with cancer. A systematic search of PubMed, EMBASE, Cochrane Library databases, ASCO, and ESMO abstracts were conducted. Randomized controlled trials (RCTs) that compared safety profile of EGFR‐TKIs with placebo were included. The end points included treatment‐related adverse events (AEs), treatment discontinuation, and toxic death. Twenty‐eight RCTs containing 17,800 patients were included. The analyses showed that the most frequently observed all‐grade AEs in patients treated with EGFR‐TKIs were diarrhea (53.7%), rash (48.6%), mucositis (46.5%), alanine aminotransferase (ALT) increased (38.9%), and skin reaction (35.2%). The most common high‐grade (grade ≥3) AEs were mucositis (14.8%), pain (8.2%,), metabolism and nutrition disorders (7.4%), diarrhea (6.2%), dyspnea (6.1%), and hypertension (6.1%). The incidence of serious AEs, treatment discontinuation, and toxic death due to AEs were 18.2%, 12.36%, and 3.0%, respectively. Pooled risk ratio (RR) showed that the use of EGFR‐TKIs was associated with an increased risk of developing AEs. Subgroup analysis indicated that the risk of AEs varied significantly according to tumor type, generation line, and drug type. Our meta‐analysis indicates EGFR‐TKIs was associated with a significant increased risk of a series of unique AEs. Early detection and proper management of AEs are important to reduce morbidity, avoid treatment discontinuation, and improve patient quality of life. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? The safety profile of epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) varied in different trials, and has not been systemically investigated. WHAT QUESTION DID THIS STUDY ADDRESS? We conducted this meta‐analysis of randomized control trials (RCTs) to provide a comprehensive evaluation of adverse event in patients with cancer receiving EGFR‐TKIs. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Our meta‐analysis indicates EGFR‐TKIs was associated with a significant increased risk of a series of unique adverse events (AEs). HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The integrated understanding of safety profile of EGFR‐TKIs will help in the future design of new EGFR‐TKIs with a better safety profile.

Background Bladder cancer is one of the most frequent cancers in the world. Muscle-invasive bladder cancer (MIBC) is the aggressive subtype with higher morbidity and mortality. Immune check point blockade (ICB) therapy has shown its potential for treating MIBC, but is limited due to the lack of predictive biomarkers. Methods 1601 MIBC transcriptomic profiles were obtained from 10 datasets. Unsupervised clustering of immune phenotypes in MIBC was performed based on immune-related signature genes selected by us. We analyzed the characteristics including microenvironments, metabolic pathways, and survival rates in different phenotypes. Multi-omics analysis and WGCNA plus protein-protein interaction (PPI) analysis were performed to identify hub genes of differentially expressed genes (DEGs) distinguishing phenotypes related to prognosis. The hub DEGs were further validated by real-time quantitative PCR (qPCR). A model was established and CART was employed to predict the responses of patients treated with ICB. Results Of various immune phenotypes, cluster 3C was the most “inflamed” subcluster with the best prognosis, while cluster 1A was associated with “non-inflammation” and worst prognosis. There was no intersection of hub DEGs selected by WGCNA plus PPI analysis and multi-omics analysis. WGCNA plus PPI analysis identified 5 hub genes related to the survival rate of patients, IFNG, CXCR6, IL2RB, LCK, and PSMB10. Real-time qPCR results indicated that the expression levels of 5 hub genes were significantly lower in tumors. The 5 hub genes were further utilized for prognostic score model and decision tree analysis. The areas under the curve (AUC) of the ROC curves predicting 5-year endpoint generated from the risk-based prediction model were 0.652. The mean accuracy, sensitivity, and specificity of CART for predicting stable disease/progressive disease were 70.1%, 70.0% and 71.7%. Conclusions The 5 hub genes and generated models showed the potential for predicting the prognosis for patients receiving ICB therapy. The molecular mechanisms regulating the expression of the hub genes require further studies in the future.

Objective Whether neutrophil could be a risk factor of renal impairment in rheumatoid arthritis (RA) remains unclear. Therefore, we aimed to investigate the prevalence of renal impairment in RA and determine its correlation with neutrophils. Methods We retrospectively investigated renal function of 602 RA patients in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine by estimated glomerular filtration rate (GFR). Potential risk factors for renal dysfunction were collected in all RA patients. We used univariate and multivariate logistic regression analysis to evaluate association between neutrophils and renal impairment. Results A total of 89 cases (14.8%) had renal impairment with GFR 2, and 75 cases (84.3%) were female. Compared to RA patients with normal renal function, age, white blood cell count, serum levels of triglyceride, uric acid, C-reactive protein level, erythrocyte sedimentation rate, Cystatin-C, and creatinine in those with renal impairment increased, but red blood cell count and hemoglobin level decreased (all p 7.5 × 10^9/L (OR = 1.7, 95% CI: 1.03 to 2.98), hemoglobin 360umol/l (OR = 6.1, 95%CI: 3.71 to 10.10) significantly correlated with a higher risk of renal impairment. Conclusions Neutrophil count > 7.5 × 10^9/L may be associated with a high risk of renal impairment in RA. Prospective studies are needed to verify our results.

Background Suprapancreatic lymphadenectomy is the essence of D2 radical gastric cancer surgery. The present study aimed to describe clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area. Methods The data from gastric cancer patients who underwent surgical treatment from September 2016 to December 2018 were collected. Patients were divided into clockwise modularized lymphadenectomy (CML) and traditional open gastrectomy (OG) groups according to the surgical treatment strategy. The propensity score matching method was utilized to balance the baseline characteristics between the two groups. Results Finally, 551 gastric cancer patients were included in the present study. Following propensity score matching, 106 pairs of patients in the CML group and OG group were included in the final analysis. The CML group had more total examined lymph nodes (36, IQR 28–44.74 vs. 29, IQR 29–39.5, p = 0.002) and no. 9 station nodes (2, IQR 1–5 vs. 2, IQR 1–3, p = 0.007) than the OG group. There was less intraoperative blood loss (30, IQR 20–80 ml vs. 80, IQR 50–80 ml, p p p = 0.591) and postoperative hospital stay (8, IQR 7–9 days vs. 8, IQR 7–9 days, p = 0.452) were comparable between the CML and OG groups. Conclusion Laparoscopic lymphadenectomy for gastric cancer surgery is technically demanding. Clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area can attain similar effects as traditional open surgery and without an increase in postoperative adverse events.

Background The role of surgical resection for patients with recurrent or metastatic gastrointestinal stromal tumors is still controversial. This meta-analysis aims to investigate the clinical outcomes of surgery combined with tyrosine kinase inhibitors among patients with recurrent or metastatic gastrointestinal stromal tumors. Methods We systematically searched PubMed, EMBASE, the Cochrane Library and Wanfangdata without language restriction. Random effect models were used to estimate pooled hazard ratio and the corresponding 95% confidence intervals. Subgroup analyses, sensitivity analysis and trim and fill analysis were also performed. Results A total of 1416 patient from 9 studies were finally enrolled in this meta-analysis. The summary results showed that surgery combined with tyrosine kinase inhibitors showed a tendency of a longer overall survival compared with tyrosine kinase inhibitors treatment alone (HR by random-effects model 0.68, 95% CI 0.54–0.85, I2 = 44.7%) and improved progress-free survival (HR by random-effects model 0.50,95% CI, 0.33–0.76, I2 = 17.9%). The trim and fill analysis and sensitive analysis indicated the relatively robust result. Conclusion Surgery combined with tyrosine kinase inhibitors therapy is associated with a better overall survival and progression free survival for patients with recurrent or metastatic gastrointestinal stromal tumors as compared with TKIs treatment alone.

Background Malignant growth and metastasis of gastrointestinal stromal tumors (GIST) occur in some patients even during the course of treatment, but their mechanisms remains poorly understand at the molecular level so far. Methods Profiles of protein expression in gastric GIST tissues were explored using protein microarray analysis, down-regulation of SPARCL1 (secreted protein acidic and rich in cysteine-like protein 1) was validated by RT-qPCR, western blot and immunohistochemistry. The effect of specific shRNA-induced SPARCL1 downregulation on the biological traits of GIST 882 cell was investigated. We then employed a mouse xenograft model to investigate whether the low-expression of SPARCL1 impact the metastasis ability of GIST cells in vivo. Results SPARCL1 was significantly downregulated in the gastric GIST with high-grade malignance as compared with low-grade malignance, its expression was closely correlated with tumor size, mitotic index, distant metastasis at the time of initial diagnosis and tumor progression of GIST (P

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

We present an approach that realizes the ground state cooling of the membrane-in-middle optomechanical system. Instead of straightforwardly using the continuous-wave (CW) or pulsed external drives, we consider the combinations of them for having a more efficient cooling process. Due to the dynamical nature of the joint action of both CW and pulse fields, it is necessary to explore the real-time evolutions of the system under various conditions, from which the optimal cooling can be found. Given such setup, the cooling limit previously discovered for the simple optomechanical systems under a single CW drive can be easily broken. The achieved cooling effect indicated by a defined cooling rate is one or more order lower than the cooling limit of a simple optomechanical systems, thus providing an efficient way of ground state cooling. Furthermore, the ground state cooling can be realized for a membrane with much lower mechanical quality factor and with the external drives of the lower intensities, to considerably relax the requirements for optomechanical cooling with the current experimental technology.

This paper describes the preparation of nanoarrays composed of silver nanoparticles (AgNPs: 20–50 nm) for use as surface-enhanced Raman scattering (SERS) substrates. The AgNPs were grown on porous anodic aluminum oxide (AAO) templates by electrochemical plating, and the inter-channel gap of AAO channels is between 10 and 20 nm. The size and interparticle gap of silver particles were adjusted in order to achieve optimal SERS signals and characterized by scanning electron microscopy, atomic force microscopy, and Raman spectroscopy. The fluctuation of SERS intensity is about 10–20% when measuring adenine solutions, showing a great reproducible SERS sensing. The nanoparticle arrays offer a large potential for practical applications as shown by the SERS-based quantitative detection and differentiation of adenine (A), thymine (T), cytosine (C), guanine (G), β-carotene, and malachite green. The respective detection limits are

Background Preoperative imatinib mesylate (IM) treatment has not yet been standardized. Here, we aim to further explore such therapy on patients with gastrointestinal stromal tumors (GIST) retrospectively. Methods Patients experiencing preoperative IM were identified from January 2009 to February 2015. Results A total of 28 GIST patients were identified. The patients received preoperative IM treatment for a median length of 13.5 months, ranging from 5 to 37 months. PR and SD were observed in 24 (85.7%) and 4 (15.3%) patients, respectively. The tumor shrinkage occurred predominantly within 6 to 12 months, and slight tumor shrinkage could be observed after 12 months in certain patients. Nineteen patients (67.9%) received surgery, and R0 resection was acquired in 18 (94.7%) patients. The initial mean maximum diameter was 10.5 (5.2 to 19.0) cm and decreased to 5.9 (2.7 to 19.0) cm after preoperative treatment with a median length of 12 (ranging from 5 to 36) months (P

// Chaoyong Shen 1, * , Yuan Yin 1, * , Huijiao Chen 2 , Sumin Tang 1 , Xiaonan Yin 1 , Zongguang Zhou 1, 3 , Bo Zhang 1 , Zhixin Chen 1 1 Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China 2 Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China 3 Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China * These authors have contributed equally to this work Correspondence to: Zongguang Zhou, email: zhou767@163.com Bo Zhang, email: hxwcwk@126.com Keywords: neuroendocrine tumors, colorectal, prognosis, WHO classifications, ENETS TNM systems Received: August 23, 2016 Accepted: November 08, 2016 Published: November 26, 2016 ABSTRACT Background/Aims: This study evaluated and compared the clinical and prognostic values of the grading criteria used by the World Health Organization (WHO) and the European Neuroendocrine Tumors Society (ENETS). Moreover, this work assessed the current best prognostic model for colorectal neuroendocrine tumors (CRNETs). Results: The 2010 WHO classifications and the ENETS systems can both stratify the patients into prognostic groups, although the 2010 WHO criteria is more applicable to CRNET patients. Along with tumor location, the 2010 WHO criteria are important independent prognostic parameters for CRNETs in both univariate and multivariate analyses through Cox regression ( P

The uncertainty relation, as one of the fundamental principles of quantum physics, captures the incompatibility of noncommuting observables in the preparation of quantum states. In this work, we derive two strong and universal uncertainty relations for $N(N\ge2)$ observables with discrete and bounded spectra, one in multiplicative form and the other in additive form. To verify their validity, for illustration, we implement in the spin-1/2 system an experiment with single-photon measurement. The experimental results exhibit the validity and robustness of these uncertainty relations, and indicate the existence of stringent lower bounds., Comment: 9 pages, 5 figures. Slightly extended

Background 12-Lipoxygenase (12-LOX) plays a major role in the progression and metastasis of various types of cancer. In gastric cancer (GC), the expression level of 12-LOX is significantly up-regulated; however, its function, and underlying mechanism of action remain unclear. Methods The mRNA and protein expression levels of 12-LOX were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses, respectively, in GC cell lines. 12-LOX expression was stably up-regulated using lentiviral vector in BGC823 and MGC803 cells, and cell-counting kit-8 (CCK8), colony formation, and invasion assays were performed to verify the function of 12-LOX in proliferation and metastasis. In addition, the expression levels of epithelial-mesenchymal transition (EMT) differentiation markers and downstream targets of the Wnt/β-catenin signaling pathway were examined by Western blotting. A nude mouse model of tumor growth and metastasis was established to investigate the role of 12-LOX in vivo. Results Our findings demonstrate that 12-LOX mRNA and protein were highly expressed in GC cell lines. 12-LOX overexpression promoted GC cell proliferation, migration, and invasion both in vitro and in vivo. In addition, up-regulation of 12-LOX promoted the EMT in GC cells, as reflected by a decrease in E-cadherin expression and an increase in N-cadherin and Snail expression. 12-LOX overexpression in GC cells also increased the expression of multiple downstream targets of the Wnt/β-catenin signaling pathway. Conclusion These findings revealed that 12-LOX functions as an oncogene in promoting GC cell proliferation and metastasis in vitro and in vivo. In addition, 12-LOX might regulate the EMT via the Wnt/β-catenin signaling pathway, indicating a potential role for 12-LOX as a target in GC treatment.

Tenascin-C (TNC), an extracellular matrix glycoprotein, has been implicated in progression of various types of cancer. However, few reports exist on TNC expression in gastrointestinal stromal tumors (GISTs). We here attempted to investigate the expression pattern and prognostic significance of TNC in gastric GISTs. We studied TNC expression in 122 gastric GISTs tissue samples by immunohistochemistry, and examined the correlations of TNC expression with clinicopathological parameters and survival of gastric GISTs. The TNC-high expression was observed in 30 (24.6%) of 122 of gastric GISTs. The high levels of TNC expression in gastric GISTs was significantly associated with tumor size (P

Background The efficacy of intravenous acetaminophen in multimodal pain management in patients undergoing total knee arthroplasty (TKA) is controversial. The purpose of this meta-analysis was to compare the efficacy of intravenous acetaminophen versus placebo in TKA. Methods Randomized controlled trials (RCTs) or retrospective cohort studies (RCSs) concerning related topics were retrieved from PubMed (1996–June 2018), Embase (1980–June 2018), and the Cochrane Library (CENTRAL June 2018). Any studies comparing intravenous acetaminophen with a placebo were included in this meta-analysis. Meta-analysis results were collected and analyzed by Stata 12.0. Subgroup analysis was performed according to the general characteristics of the patients. Results In total, the patients from six studies met the inclusion criteria. Our meta-analysis results indicated that compared with a control group, intravenous acetaminophen was associated with reductions in total morphine consumption and visual analogue scale (VAS) score at postoperative day (POD) 3. However, there was no significant difference in morphine consumption at POD 1 or in VAS at POD 1 or POD 2. Moreover, there was no significant difference in the length of hospital stay. Conclusions Based on our results, intravenous acetaminophen in multimodal management has shown better efficacy in pain relief at POD 3 and has morphine-sparing effects. High-quality studies with more patients are needed in the future. Electronic supplementary material The online version of this article (10.1186/s13018-018-0950-7) contains supplementary material, which is available to authorized users.

The role of extranodal metastasis (ENM) in TNM stage in gastric carcinoma (GC) is controversial. This study was aimed to make a detailed investigation of the prognostic significance and the role in TNM stage of ENM in GC. The patients with primary GC, who underwent gastrectomy with curative intention in West China Hospital from January 2005 to December 2011, were retrospectively enrolled. The prognosis and clinicopathological traits were compared between ENM positive (ENMP) and negative (ENMN) groups in all patients, TNM I-II, III and IV stages, respectively. The significance of the number and the role in TNM stage of ENM were also assessed. In our study, 1457 patients were enrolled, with 1324 (90.9%) in ENMN group and 133 (9.1%) in ENMP group. ENMP group had significantly more advanced GC and worse prognosis (all p2 subgroup had remarkably larger tumor size (p=0.002) and more advanced N stage (p=0.016) than ENM=1-2 subgroup. The number of ENM was an independent prognostic factor in ENMP group (p=0.029). The prognosis of ENM>2 in TNM I-III stages was significantly worse than ENMN patients in TNM III stage. The C-index of TNM stage plus the number of ENM was significantly higher than that of current TNM stage alone (p=0.005). In conclusion, the patients in ENMP subgroup had more advanced GC and worse prognosis than those in ENMN subgroup. It might be more reasonable to categorize ENM>2 into TNM IV stage.

// Lin-Yong Zhao 1,2,3,* , Xiao-Long Chen 1,2,* , Yi-Gao Wang 1,2,3,* , Yue Xin 3 , Wei-Han Zhang 1,2,3 , Yin-Su Wang 3 , Xin-Zu Chen 1,2 , Kun Yang 1,2 , Kai Liu 1,2 , Lian Xue 1,2,3 , Bo Zhang 1 , Zhi-Xin Chen 1 , Jia-Ping Chen 1 , Zong-Guang Zhou 1 and Jian-Kun Hu 1,2 1 Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China 2 Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China 3 West China School of Medicine, Sichuan University, Chengdu, China * These authors have contributed equally to this work Correspondence to: Jian-Kun Hu, email: // Keywords : predictive model; gastric cancer; tumor size; lymphovascular invasion; lymph nodes count Received : February 15, 2016 Accepted : July 18, 2016 Published : August 04, 2016 Abstract Background: Various factors may affect the clinical prognosis of lymph node-negative gastric cancer (GC) patients. This study aimed to provide evaluable prognostic information of combination of tumor size (Ts), lymph nodes count (LNs) and lymphovascular invasion (LVI) in lymph node-negative GC patients. Methods: A total of 1,019 node-negative GC patients were enrolled in this retrospective study from 2000 to 2010. The cutoff points of Ts and LNs were determined using X-tile and patients were randomly categorized into training and validation sets by the sample size ratio 1:1. The clinicopathologic characteristics were analyzed and survival prognostic factors were identified, whereas the survival prediction accuracy was also compared by C-index during the different independent prognostic factors. Results: The cutoff points for Ts were 3cm and 5cm, while 14 was the cutoff point for LNs. Age, T stage, Ts, LNs and LVI were identified as independent prognostic factors in node-negative GC patients, and a new prognostic predictive model, TsNL staging system which was composed of Ts, LNs and LVI, was proposed in this study. Compared with T staging system, significant improvement of predictive accuracy for TsNL system was found. Furthermore, nomogram based on TsNL was more accurate in prognostic prediction than that based on Ts, LNs and LVI, separately. Conclusions: Age, T stage, Ts, LNs and LVI were independent prognostic factors in lymph node-negative GC patients. The TsNL staging system, composed of Ts, LNs and LVI, which was closely associated with clinicopathologic features, may improve the prognostic prediction accuracy in node-negative GC patients.

// Lin-Yong Zhao 1, 2, 3, * , Yuan Yin 1, * , Xue Li 3 , Chen-Jing Zhu 3 , Yi-Gao Wang 1, 2, 3 , Xiao-Long Chen 1, 2 , Wei-Han Zhang 1, 2, 3 , Xin-Zu Chen 1, 2 , Kun Yang 1, 2 , Kai Liu 1, 2, 3 , Bo Zhang 1 , Zhi-Xin Chen 1 , Jia-Ping Chen 1 , Zong-Guang Zhou 1 , Jian-Kun Hu 1, 2 1 Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China 2 Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, China 3 West China School of Medicine, Sichuan University, China * These authors have contributed equally to this work Correspondence to: Jian-Kun Hu, email: hujkwch@126.com Keywords: early gastric cancer, nomogram, lymph node metastasis, prediction, tumor markers Received: April 12, 2016 Accepted: July 10, 2016 Published: July 20, 2016 ABSTRACT Predicting lymph node metastasis (LNM) accurately is of great importance to formulate optimal treatment strategies preoperatively for patients with early gastric cancer (EGC). This study aimed to explore risk factors that predict the presence of LNM in EGC. A total of 697 patients underwent gastrectomy enrolled in this study, were divided into training and validation set, and the relationship between LNM and other clinicopathologic features, preoperative serum combined tumor markers (CEA, CA19-9, CA125) were evaluated. Risk factors for LNM were identified using logistic regression analysis, and a nomogram was created by R program to predict the possibility of LNM in training set, while receiver operating characteristic (ROC) analysis was applied to assess the predictive value of the nomogram model in validation set. Consequently, LNM was significantly associated with tumor size, macroscopic type, differentiation type, ulcerative findings, lymphovascular invasion, depth of invasion and combined tumor marker. In multivariate logistic regression analysis, factors including of tumor size, differentiation type, ulcerative findings, lymphovascular invasion, depth of invasion and combined tumor marker were demonstrated to be independent risk factors for LNM. Moreover, a predictive nomogram with these independent factors for LNM in EGC patients was constructed, and ROC curve demonstrated a good discrimination ability with the AUC of 0.847 (95% CI: 0.789-0.923), which was significantly larger than those produced in previous studies. Therefore, including of these tumor markers which could be convenient and feasible to obtain from the serum preoperatively, the nomogram could effectively predict the incidence of LNM for EGC patients.

This study aimed to evaluate the prognostic significance of node ratio (Nr), the ratio of metastatic to retrieved lymph nodes, and to investigate whether a modified staging system based on Nr can improve prognostic ability for gastric cancer patients following gastrectomy. A total of 2572 patients were randomly divided into training set and validation set, and the cutoff points for Nr were produced using X-tile. The relationships between Nr and other clinicopathologic factors were analyzed, while survival prognostic discriminatory ability and accuracy were compared among different staging systems by AIC and C-index in R program. Patients were categorized into four groups as follows: Nr0, Nr1: 0.00-0.15, Nr2: 0.15-0.40 and Nr3: > 0.40. Nr was significantly associated with clinicopathologic factors including macroscopic type, tumor differentiation, lymphovascular invasion, perineural invasion, tumor size, T stage, N stage and TNM stage. Besides, for all patients, Nr and TNrM staging system showed a smaller AIC and a larger C-index than that of N and TNM staging system, respectively. Moreover, in subgroup analysis for patients with retrieved lymph nodes < 15, Nr was demonstrated to have a smaller AIC and a larger C-index than N staging system. Furthermore, in validation analysis, Nr, categorized by our cutoff points, showed a larger C-index and a smaller AIC value than those produced in previous studies. Nr could be considered as a reliable prognostic factor, even in patients with insufficient (< 15) retrieved lymph nodes, and TNrM staging system may improve the prognostic discriminatory ability and accuracy for gastric cancer patients undergoing radical gastrectomy.

Capillary invasion (CI) has been found to play an important role in metastasis and recurrence of gastric adenocarcinoma (GAC). However, the prognostic significance of CI is still controversial. From January 2005 to December 2011, 1398 patients with GAC who underwent gastrectomy were retrospectively enrolled and divided into CI (+) and CI (−) groups. Clinicopathological features and survival outcomes were compared between these groups. In our study, 227 (16.2%) patients were CI (+). Patients with CI (+) had significantly more advanced tumors and worse prognosis than those with CI (−) (p < 0.001). CI was demonstrated as an independent prognostic factor (p = 0.023) in patients with GAC. When stratified by TNM stage, the prognosis of CI (+) group in stage III was remarkably worse than CI (−) group (p = 0.006), while the differences were not significant in stage I–II and stage IV (both p > 0.05). The nomograms indicated that CI was part of the individual prognostic prediction system. The predictive accuracy of CI and other characteristics was better than TNM alone (p < 0.001). Our finding suggested that CI was an independent prognostic factor in patients with GAC, and the nomogram based on CI and other clinicopathological factors was a valuable and accurate tool in individual prognostic prediction.

Background. The impact of perioperative blood transfusion on the prognosis of gastric adenocarcinoma patients is still controversial. The aim of this study was to elucidate the impact of perioperative blood transfusion on postoperative complications and prognosis of patients who underwent gastrectomy for gastric adenocarcinoma with different levels of preoperative hemoglobin value (POHb).Method. From 2003 to 2011, 1199 patients who underwent curative gastrectomy were retrospectively enrolled and followed up to December 2014. Clinicopathological features and survival outcomes were compared between transfused and nontransfused patients.Results. In this study, transfused patients had more postoperative complications than nontransfused ones (P=0.002). In survival analysis, the difference was not significant between transfused and nontransfused patients with POHb between 70 and 100 g/L (P=0.191). However, in patients with POHb >100 g/L, transfused patients had significantly worse prognosis (P<0.001), especially in TNM III stage patients (P=0.002). And intraoperative blood transfusion predicted poor prognosis (P=0.001).Conclusion. Perioperative blood transfusion might lead to poor survival in gastric adenocarcinoma patients with POHb >100 g/L and transfused patients had more postoperative complications; thus it is better to refrain from unnecessary perioperative blood transfusion especially intraoperative transfusion.

Gastric and esophageal cancers are 2 of the most common malignancies in the world. More than 70% of gastric cancer cases and deaths occur in developing countries, and most occur in Eastern Asia.1 There have been distinct changes in the incidences of cancer at different anatomical subsites of the stomach in Western countries.2–4 Many population-based studies showed that the incidence rates of adenocarcinoma of the esophagus and esophagogastric junction (EGJ) were increased in Western countries and Asian countries, such as Japan and Korea.2–8 Although squamous cell carcinoma of the esophagus is still predominant, more than half of newly diagnosed tumors are adenocarcinoma of distal esophagus and EGJ in Western countries and Japan.2–4,6 Incidence of adenocarcinoma at the upper third of the stomach and EGJ has increased over the past 2 decades, with a rate which has exceeded that at any other site of stomach.2,4 In contrast, incidence of adenocarcinoma at distal stomach has gradually declined over the past 50 years.3 However, investigations on changes of esophagogastric junction adenocarcinoma (EGJA) in China remains sparse. Gastroesophageal reflux disease (GERD) was one of the most common gastrointestinal diseases in Europe and the United States with prevalence rates of 10% to 25% in population-based studies.9,10 Reports from many other regions have also demonstrated an increase in the prevalence of GERD.11,12 Some of those with GERD may develop Barrett esophagus, which can lead to esophageal adenocarcinoma. In addition, the prevalence of GERD was also found to be closely associated with the risk of EGJA in some Asian countries.13 Patients with Barrett esophagus need more intensive screening and surveillance for EGJA. Therefore, it is necessary to understand the changes of GERD and EGJA in China over time. However, there were rare reports that simultaneously assessed the trends of EGJA and GERD in China over time. A study by Zhou et al14 showed that there was an increasing trend of gastric cardia cancer over a 12-year period in a northwest province of China. With the increasing acceptance of Siewert's definition of EGJA, more and more researchers have studied this kind of clinicopathological entity.15 However, there have been few investigations into the change over time of 3 subtypes of EGJA in China. The volume of surgeries done for gastric and esophageal cancers at our institution is large, and the sources of patients come from the Western China, which may serve as a reference for a large population-based study. In this study, we aimed to evaluate the changes of clinicopathological features and surgical treatment of EGJA on the basis of the Siewert classification16 and the prevalence of GERD among the surgical patients with EGJA in a high-volume Chinese hospital during 1988–2012.

Nutritional and immune status is important to the prognosis of patients with gastric carcinoma (GC). Here, we evaluated the prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) in patients with GC. From January 2005 to December 2011, 1332 patients with GC who underwent gastrectomy were randomly divided into the training (n = 888) and the validation sets (n = 444) by X-tile according to the sample size ratio 2:1. The cut-point of HALP was 56.8 and the patients were subsequently subdivided into HALP < 56.8 and HALP ≥ 56.8 groups in both two sets. Multivariate analysis revealed that gender (p < 0.001, p < 0.001), tumor size (p = 0.003, p = 0.035) and T stage (p < 0.001, p = 0.044) were independently related to HALP both in the training and the validation sets. Kaplan-Meier (p < 0.001, p = 0.003) and Cox regression (p = 0.043, p = 0.042) showed that the prognosis of HALP ≥ 56.8 group was significantly better than that of HALP < 56.8 group both in two sets (p < 0.001, p < 0.001). Nomograms of these two sets based on HALP were more accurate in prognostic prediction than TNM stage alone. Our findings suggested that HALP was closely associated with clinicopathological features and was an independent prognostic factor in GC patients. Nomogram based on HALP could accurately predict the prognosis of GC patients.

To identify significant clinical and CT features for the differentiation of gastrointestinal stromal tumors (GISTs) from leiomyomas in the esophagogastric junction (EGJ). One hundred thirty six patients with pathologically proven GISTs (n = 87) and leiomyomas (n = 49) in the EGJ were enrolled. And preoperative CT images were available in 73 GISTs cases and 34 leiomyoma cases. Two radiologists reviewed the CT images by consensus with regard to tumor size, shape, growth pattern, surface, enhancement pattern, enhancement degree, attention at each phasic image and the presence of surface ulcer, calcification, and intralesional low attention. Eight significant clinical and CT features were identified for differentiating GISTs from leiomyomas: older age (>46.5 years), tumor long diameter >4.5 cm, heterogeneous enhancement, high degree enhancement, mean CT attenuation >69.2 HU, presences of intralesional low attenuation and surface ulcer, absences of calcification (P 46.5 years), tumor long diameter >4.5 cm, heterogeneous enhancement, high degree enhancement, mean CT attenuation >69.2 HU, presences of intralesional low attenuation and surface ulcer, absence of calcification are significant features highly suggestive of GISTs in differentiation from leiomyomas in the EGJ.

Glucocorticoids are the most common cause of glucocorticoid‑induced osteoporosis (GIOP). Moreover, the role of circular RNAs (circRNAs) in the regulation of bone metabolism remains unclear. Therefore, in the present study, it was hypothesized that hsa_circ_0006393 may play an important role in GIOP. To investigate the role of circRNAs in GIOP, treatment with dexamethasone or transfection with a vector overexpressing hsa_circ_0006393 were performed using in vitro cell and in vivo mouse models. Reverse transcription‑quantitative PCR, fluorescence in situ hybridization and western blotting were performed to investigate the function of hsa_circ_0006393 in vitro. In addition, the effects of hsa_circ_0006393 on osteogenesis were investigated. Dual‑energy X‑ray absorptiometry analysis was performed to examine the osteogenic potential of hsa_circ_0006393 in vivo. Moreover, the mechanism underlying hsa_circ_0006393‑mediated bone metabolism regulation via the microRNA (miR)‑145‑5p/forkhead box O1 (FOXO1) pathway was investigated. The present results suggested that the expression level of hsa_circ_0006393 was decreased in patients with GIOP. Furthermore, the overexpression of hsa_circ_0006393 increased the expression level of genes associated with osteogenesis. Moreover, hsa_circ_0006393 was identified to be localized mainly in the cytoplasm and nucleus of bone marrow mesenchymal stem cells. miR‑145‑5p was found to be directly targeted by hsa_circ_0006393. Collectively, hsa_circ_0006393 increases the expression levels of osteogenic genes during bone remodeling by sponging miR‑145‑5p and upregulating FOXO1.

Retroperitoneal desmoid-type fibromatosis (RPDF) is a rare mesenchymal neoplasm, and it covers a broad spectrum of aggressive monoclonal, fibroblastic proliferation. There is no evidence-based or established optimal treatment available for this intriguing disease yet. Therefore, we here investigated the clinicopathological characteristics, surgical, and survival outcomes in RPDF among Chinese patients. Patients with histologically confirmed RPDF were retrospectively studied from 2010 to 2018 within the West China Hospital of Sichuan University. Demographics, clinicopathological characteristics, treatment, and survival outcome data were collected. Of the 29 cases of RPDF, 19 were females. Tumor diameter ranged from 4 to 40 cm, with a median of 10 cm. Of these patients, surgical resection was the primary treatment adopted for RPDF in 26 cases; while 3 patients underwent watchful waiting. In surgical group, complete and incomplete macroscopic resection was achieved in 21 (80.77%) and 6 (19.23%) cases, respectively. Totally, 21 (80.77%) cases underwent multi-visceral resection. With a median follow-up duration of 48 months, 11 patients experienced tumor progression for the entire cohort. Tumor progression was observed for those patients with incomplete and complete macroscopic resection in 2/5 (40.0%) and 6/21 (28.6%) cases, respectively. In the watchful waiting group, there were no documented cases of RPDF regression. The progression-free survival rate was 86.1%, 71.5%, and 62.3% at 1-, 2-, and 3-years, respectively. RPDFs are rare types of tumor, which have characteristically varied natural histories. Surgical resection had a relative favorable outcome, but some patients were associated with burden of significant surgical complications.

Background: The choice of anastomosis methods including Billroth I, Billroth II, and Roux-en-Y after a distal gastrectomy is still controversial. The conventional meta-analyses assessing 2 alternative treatments were not powered to compare differences in clinical outcomes. To guide treatment decisions in patients with gastric cancer (GC) after distal gastrectomy, we did a systematic review and network meta-analysis to identify the best reconstruction method. Methods: We systematically searched PubMed, EMBASE, the Cochrane Library for randomized controlled trials comparing the outcomes of Billroth I, Billroth II, or Roux-en-Y reconstruction after distal subtotal gastrectomy for patients with GC, then we performed a direct meta-analysis and Bayesian network meta-analysis to pooled odds ratios (OR) or weighted mean differences (WMD) with 95% credible intervals (CrI) with random effects model. The node-splitting method was used to assess the inconsistency. We estimated the potential ranking probability of treatments by calculating the surface under the cumulative ranking curve for each intervention. Results: Nine studies involving 1161 patient were included in the network meta-analysis. Statistical significance was reached for the comparisons of Roux-en-Y versus Billroth I reconstruction (WMD 37, 95% Crl: 22–51) and Billroth II versus Billroth I reconstruction (WMD 25, 95% Crl: 5.8–43) for operation time; and Roux-en-Y versus Billroth I reconstruction (WMD 26, 95% Crl: 2.1–68) for intraoperative blood loss; and Roux-en-Y versus Billroth I reconstruction (OR 3.4, 95% Crl: 1.1–13) for delayed gastric emptying. Roux-en-Y reconstruction was superior to Billroth I and Billroth II reconstruction in terms of frequency of bile reflux (OR 0.095, 95% Crl: 0.010–0.63; OR 0.064, 95% Crl: 0.0037–0.84, respectively) and the incidence of remnant gastritis (OR 0.33, 95% Crl: 0.16–0.58; OR 0.40, 95% Crl: 0.17–0.92, respectively). Conclusion: Roux-en-Y reconstruction is superior to Billroth I and Billroth II reconstruction in terms of preventing bile reflux and remnant gastritis, Billroth I and Billroth II anastomosis could be considered as the substitute in consideration of technical simplicity. As for postoperative morbidity and the advantage of physiological food passage, Billroth I method is the choice.

Different adjuvant treatments are available for patients with gastric cancer, but conventional meta-analyses performing direct comparisons between two alternative treatments did not have enough power to compare all the adjuvant treatments. Thus, we did a network meta-analysis summarizing the direct and indirect comparisons to identify the optimum treatment. We systematically searched for RCTs of adjuvant treatments for gastric cancer comparing two or more of the following treatments: surgery alone, radiotherapy with fluoropyrimidine, S-1-based regimens, and XELOX. The treatments offering available indirect evidence to investigate the comparative effectiveness of adjuvant treatments mentioned above were also included. Then we performed a Bayesian network meta-analysis to summarize the direct and indirect comparisons. We estimated hazard ratios with 95% credible intervals (CrI) for OS and DFS. 11 eligible RCTs (5620 patients) were included in the network meta-analysis. Radiotherapy with fluorouracil (5-FU/RT), S-1-based regimens, and XELOX significantly improved OS as compared with surgery alone [(HR = 0.75 with 95% CrI: 0.63–0.89), (HR = 0.63 with 95% CrI: 0.52–0.76), and (HR = 0.66 with 95% CrI: 0.51–0.85), respectively]. No treatment was clearly superior to others; however, S-1-based regimes and XELOX showed a statistically non-significant trend to better survival as compared with 5-FU/RT. S-1-based chemotherapy and XELOX are likely to be the most effective adjuvant treatments for patients with resected gastric cancer. 5-FU alone provided little survival benefits as compared with surgery alone. Further clinical trials may be required to investigate S-1-based and XELOX-based adjuvant treatment strategies.

The uncertainty relation is a distinguishing feature of quantum theory, characterizing the incompatibility of noncommuting observables in the preparation of quantum states. Recently, many uncertainty relations were proposed with improved lower bounds and were deemed capable of incorporating multiple observables. Here we report an experimental verification of seven uncertainty relations of this type with single-photon measurements. The results, while confirming these uncertainty relations, show as well the relative stringency of various uncertainty lower bounds., slightly extended. To appear in PRA