Comparison of metastasis and prognosis between early-onset and late-onset hepatocellular carcinoma: A population-based study.

Background: While hepatocellular carcinoma (HCC) represents a highly heterogeneous disease with variable oncogenesis mechanisms and biological features, little is understood about differences in distant metastasis (DM) and prognosis between early-onset and late-onset HCC. This study defined early-onset disease as cancer diagnosed at age younger than 50 years and aimed to present a comprehensive analysis to characterize these disparities based on age. Methods: Information of HCC patients was retrospectively collected from the SEER database and our hospital. Patient demographics, tumor characteristics, and survival were compared between the two groups. A 1:1 propensity score matching (PSM) was adopted to adjust confounding factors. Logistic and cox analysis were utilized to explore risk factors of DM and prognosis, respectively. Besides, the survival differences were assessed by the Kaplan-Meier curve and log-rank test. Results: In total, 19187 HCC patients obtained from the SEER database and 129 HCC patients obtained from our own center were enrolled. Among 19187 patients with HCC, 3376 were identified in the matched cohort, including 1688 early-onset patients and 1688 late-onset patients. Compared with late-onset HCC, early-onset HCC was more likely to occur in female (25.2% vs. 22.9%, P = 0.030), have large tumors (>10.0 cm, 24.1% vs. 14.6%, P = 0.000), harbor poorly differentiated/undifferentiated cancers (17.0% vs. 14.0%, P = 0.003), present advanced clinical stage (T3+T4, 33.7% vs. 28.5%; N1, 9.2% vs. 6.7%; P = 0.000), and develop DM (13.0% vs. 9.5%, P = 0.000). After adjustment for confounders by PSM, we discovered that early-onset HCC remained an independent risk factor for DM. However, combined with Kaplan-Meier curve and cox analysis, early-onset HCC was an independent favorable predictor of survival. We validated these data on an independent cohort from our hospital. Conclusion: In this population-based study, despite developing DM more frequently, early-onset HCC exhibited a superior prognosis than late-onset HCC. Nevertheless, further research is warranted to understand the underlying aetiologic basis for the disparities.

O-GlcNAcylation promotes the progression of nonalcoholic fatty liver disease by upregulating the expression and function of CD36.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) and its progressive variant, nonalcoholic steatohepatitis (NASH), constitute a burgeoning worldwide epidemic with no FDA-approved pharmacotherapies. The multifunctional immunometabolic receptor, fatty acid translocase CD36 (CD36), plays an important role in the progression of hepatic steatosis. O-GlcNAcylation is a crucial posttranslational modification that mediates the distribution and function of CD36, but its involvement in NAFLD remains poorly understood. METHODS: O-GlcNAcylation and CD36 expression were evaluated in human liver tissues obtained from NASH patients and normal control. Mice with hepatocyte-specific CD36 knockout were administered adeno-associated viral vectors expressing wild-type CD36 (WT-CD36) or CD36 O-GlcNAcylation site mutants (S468A&T470A-CD36) and were provided with a high-fat/high-cholesterol (HFHC) diet for 3 months. RT-qPCR analysis, immunoblotting, dual-luciferase reporter assays, chromatin immunoprecipitation, and coimmunoprecipitation were performed to explore the mechanisms by which O-GlcNAcylation regulates CD36 expression. Membrane protein extraction, immunofluorescence analysis, site-directed mutagenesis, and fatty acid uptake assays were conducted to elucidate the impact of O-GlcNAcylation on CD36 function. RESULTS: O-GlcNAcylation and CD36 expression were significantly increased in patients with NASH, mouse models of NASH, and palmitic acid-stimulated hepatocytes. Mechanistically, the increase in O-GlcNAcylation facilitated the transcription of CD36 via the NF-κB signalling pathway and stabilized the CD36 protein by inhibiting its ubiquitination, thereby promoting CD36 expression. On the other hand, O-GlcNAcylation facilitated the membrane localization of CD36, fatty acid uptake, and lipid accumulation. However, site-directed mutagenesis of residues S468 and T470 of CD36 reversed these effects. Furthermore, compared with their WT-CD36 counterparts, HFHC-fed S468A&T470A-CD36 mice exhibited decreases in systemic insulin resistance, steatosis severity, inflammation and fibrosis. Pharmacological inhibition of O-GlcNAcylation and CD36 also mitigated the progression of NASH. CONCLUSIONS: O-GlcNAcylation promotes the progression of NAFLD by upregulating CD36 expression and function. Inhibition of CD36 O-GlcNAcylation protects against NASH, highlighting a potentially effective therapeutic approach for individuals with NASH.

DDX3X interacts with SIRT7 to promote PD-L1 expression to facilitate PDAC progression.

Pancreatic ductal adenocarcinoma (PDAC) is recognized as the most aggressive and fatal malignancy. A previous study reported that PDAC patients who exhibit elevated levels of DDX3X have a poor prognosis and low overall survival rate. However, the underlying molecular mechanism remains unclear. This study aimed to investigate the specific roles of DDX3X in PDAC. Multiple bioinformatics analyses were used to evaluate DDX3X expression and its potential role in PDAC. In vitro and in vivo studies were performed to assess the effects of DDX3X on PDAC cell growth. Furthermore, Western blotting, quantitative PCR, immunohistochemistry, immunofluorescence, mass spectrometry, coimmunoprecipitation and multiplexed immunohistochemical staining were conducted to identify the specific regulatory mechanism in PDAC. The results verified that DDX3X expression is notably upregulated in the tumor tissue vs. normal tissue of PDAC patients. DDX3X knockdown markedly suppressed the proliferation, invasion and migration of PDAC cells in vitro and inhibited tumor growth in vivo. Conversely, overexpression of DDX3X induced the opposite effect. Further studies supported that the DDX3X protein can associate with sirtuin 7 (SIRT7) to stimulate PDAC carcinogenesis and progression. Furthermore, SIRT7 inhibition significantly impeded DDX3X-mediated tumor growth both ex vivo and in vivo. The results also revealed that programmed death ligand 1 (PD-L1) expression is positively correlated with DDX3X expression. These results reveal significant involvement of the DDX3X-SIRT7 axis in the initiation and advancement of PDAC and offer previously undiscovered therapeutic options for PDAC management.

Protective and Adverse Roles of DDX3X in Different Cell Types in Nonalcoholic Steatohepatitis Progression.

Persistent hepatic cellular metabolic stress and liver inflammatory stimuli are key signatures of nonalcoholic steatohepatitis (NASH). DDX3X is a vital molecule involved in cell fate decisions in both pro-survival stress granule (SG) and pro-death NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly in response to stress signals. However, the role of DDX3X in NASH remains unclear. We characterized the cell type-specific roles of DDX3X in NASH. Human liver tissues from NASH patients and normal control subjects were collected to assess DDX3X expression and distribution. Nutritional steatohepatitis models were constructed by feeding macrophage-specific DDX3X knockout (DDX3XΔMφ), hepatocyte-specific DDX3X knockout (DDX3XΔhep), and wild-type control (DDX3Xfl/fl) mice a high-fat and high-cholesterol (HFHC) diet, a methionine- and choline-deficient (MCD) diet, and a high-fat/high-iron/high-fructose/high-cholesterol, low-methionine, and choline-deficient (HFHIHFHC-MCD) diet. The study demonstrated that DDX3X was predominantly expressed in macrophages and hepatocytes in control liver tissues, and its expression was down-regulated in patients or mice with NASH. Compared to DDX3Xfl/fl littermates, DDX3XΔMφ mice showed improved liver histology in nutritional steatohepatitis models. Loss of macrophage DDX3X inhibited NLRP3 inflammasome-mediated pyroptosis, causing anti-inflammatory M2 polarization and alleviating hepatocyte steatohepatitic changes. DDX3XΔhep mice developed marked steatohepatitis in multiple nutritional steatohepatitis models compared to DDX3Xfl/fl littermates. DDX3X-deleted hepatocytes showed impaired SG assembly, leading to increased sensitivity and intolerance to metabolic stimulation and resultant steatohepatitis. In conclusion, DDX3X plays opposite roles in different cell types during the progression of NASH. A better understanding of the cell-specific differences in the crosstalk between SG formation and NLRP3 activation is crucial for developing prospective targeted DDX3X inhibitors for the treatment of NASH.

Hepatocyte DDX3X protects against drug-induced acute liver injury via controlling stress granule formation and oxidative stress.

Drug-induced liver injury (DILI) is the leading cause of acute liver failure (ALF). Continuous and prolonged hepatic cellular oxidative stress and liver inflammatory stimuli are key signatures of DILI. DEAD-box helicase 3, X-linked (DDX3X) is a central regulator in pro-survival stress granule (SG) assembly in response to stress signals. However, the role of DDX3X in DILI remains unknown. Herein, we characterized the hepatocyte-specific role of DDX3X in DILI. Human liver tissues of DILI patients and control subjects were used to evaluate DDX3X expression. APAP, CCl4 and TAA models of DILI were established and compared between hepatocyte-specific DDX3X knockout (DDX3XΔhep) and wild-type control (DDX3Xfl/fl) mice. Hepatic expression of DDX3X was significantly decreased in the pathogenesis of DILI compared with controls in human and mice. Compared to DDX3Xfl/fl mice, DDX3XΔhep mice developed significant liver injury in multiple DILI models. DDX3X deficiency aggravates APAP induced oxidative stress and hepatocyte death by affecting the pro-survival stress granule (SG) assembly. Moreover, DDX3X deficiency induces inflammatory responses and causes pronounced macrophage infiltration. The use of targeted DDX3X drug maybe promising for the treatment of DILI in human.

TATA-box-binding protein promotes hepatocellular carcinoma metastasis through epithelial-mesenchymal transition.

BACKGROUND: HCC characterizes malignant metastasis with high incidence and recurrence. Thus, it is pivotal to discover the mechanisms of HCC metastasis. TATA-box-binding protein (TBP), a general transcriptional factor (TF), couples with activators and chromatin remodelers to sustain the transcriptional activity of target genes. Here, we investigate the key role of TBP in HCC metastasis. METHODS: TBP expression was measured by PCR, western blot, and immunohistochemistry. RNA-sequencing was performed to identify downstream proteins. Functional assays of TBP and downstream targets were identified in HCC cell lines and xenograft models. Luciferase reporter and chromatin immunoprecipitation assays were used to demonstrate the mechanism mediated by TBP. RESULTS: HCC patients showed high expression of TBP, which correlated with poor prognosis. Upregulation of TBP increased HCC metastasis in vivo and in vitro, and muscleblind-like-3 (MBNL3) was the effective factor of TBP, positively related to TBP expression. Mechanically, TBP transactivated and enhanced MBNL3 expression to stimulate exon inclusion of lncRNA-paxillin (PXN)-alternative splicing (AS1) and, thus, activated epithelial-mesenchymal transition for HCC progression through upregulation of PXN. CONCLUSIONS: Our data revealed that TBP upregulation is an HCC enhancer mechanism that increases PXN expression to drive epithelial-mesenchymal transition.

Comparative effectiveness of different probiotics supplements for triple helicobacter pylori eradication: a network meta-analysis.

Background: Probiotics has been reported as an effective supplement for Helicobacter pylori eradication. However, knowledge of their comparative efficacy is still lacking. Aim: In this study, we used network meta-analysis of current probiotics supplement used in standard triple therapy to assess and rank their comparative effectiveness. Methods: All randomized controlled trials from three main databases (PubMed, Embase and Cochrane Library) up to April 2022 were collected and filtered to meet our criterion. We used Bayesian network meta-analysis to evaluate the eligible randomized controlled trials and gave a rank for the efficiency and incidence of side effects of each probiotics supplement. The ranking probability for each therapy was assessed by means of surfaces under cumulative ranking values. Subgroup analysis was conducted to evaluate other possible influencing factors. Results: 34 eligible randomized controlled trials entered the following meta-analysis, including 9,004 patients randomized to 10 kinds of therapies. Result showed that most probiotics added therapies had better outcomes than triple therapy, among which Bifidobacterium-Lactobacillus and Bifidobacterium-Lactobacillus-Saccharomyces adjuvant therapy could obtain comprehensive benefit with high eradication rate (78.3% and 88.2% respectively), and cause few side effects. Combination of different probiotics, adding probiotics before or after triple therapy and longer duration of probiotics can improve therapeutic effect in H.pylori infected individuals. Conclusion: For triple therapy of H.pylori infection, adding probiotics can increase eradication rate and bring protective effect. Considering the overall influence, Bifidobacterium-Lactobacillus or Bifidobacterium-Lactobacillus-Saccharomyces therapy can be a better choice in improving H.pylori eradication process.

A creatinine-based model for predicting recurrent bleeding after modified percutaneous transhepatic variceal embolization in patients with cirrhosis.

Background: Patients who survive initial esophagogastric variceal bleeding (EVB) are at an increased risk of recurrent bleeding and death; however, a reliable predictive model is lacking. We aimed to develop a model for rebleeding prediction in patients with EVB after modified percutaneous transhepatic variceal embolization (PTVE) with cyanoacrylate. Methods: A total of 122 patients with EVB who underwent PTVE from January 2015 to November 2020 were enrolled. Multivariate logistic analyses were conducted to determine independent risk factors for nomogram construction. The discrimination, calibration, and clinical utility of the nomogram were compared with the Model for End-stage Liver Disease score (MELD) and the Child-Pugh model. Risk stratification was performed according to the nomogram. Results: Rebleeding within 3 months of PTVE occurred in 32 patients (26.2%). Independent rebleeding indicators included prior history of endoscopic therapy, Child-Pugh score, partial splenic embolization, and creatinine level. The nomogram incorporating these four predictors achieved excellent calibration and discriminatory abilities, with a concordance index of 0.85, which was confirmed to be 0.83 through bootstrapping validation. The nomogram demonstrated superior discrimination and clinical applicability than the MELD and Child-Pugh models. As shown in the Kaplan-Meier curves, high-risk patients had a high probability of rebleeding (P â€‹< â€‹0.001). Conclusions: The creatinine-based nomogram had a superior ability to predict rebleeding after PTVE in patients with EVB. Risk stratification may help identify high-risk patients and lead to the earlier implementation of aggressive treatments and formulation of intensive follow-up plans.

Tumor Response and Nomogram-Based Prognostic Stratification for Hepatocellular Carcinoma After Drug-Eluting Beads Transarterial Chemoembolization.

Purpose: To explore the tumor response and propose a nomogram-based prognostic stratification for hepatocellular carcinoma (HCC) after drug-eluting beads transarterial chemoembolization (DEB-TACE). Patients and Methods: From the database of two centers, patients who received DEB-TACE as an initial treatment were enrolled and divided into the training and validation sets. The tumor response after DEB-TACE was estimated according to the Modified Response Evaluation Criteria in Solid Tumors. Using the independent survival predictors in the training set, a nomogram was constructed and validated internally and externally by measuring concordance index (C-index) and calibration. A prognostic stratification based on the nomogram was established. Results: A total of 335 patients met the inclusion criteria for the study. Alkaline phosphatase level, tumor maximum diameter, tumor capsule and portal vein invasion were interrelated with the achievement of complete release after DEB-TACE. Alpha-fetoprotein level, Child-Pugh class, tumor maximum diameter, tumor number, tumor extent and portal vein invasion were integrated into the nomogram. The nomogram demonstrated good calibration and discrimination, with C-indexes of 0.735 and 0.854 and higher area under the curve (AUC) than BCLC and CNLC staging systems in the internal and external validation sets. The prognostic stratification classified patients into three different risk groups, which had significant differences in survival, complete release and objective response rate between any two groups (P < 0.05). Conclusion: The nomogram-based prognostic stratification has a good distinction and may help to identify the patients benefiting from DEB-TACE.

Comparison of treatment strategies and survival of early-onset gastric cancer: a population-based study.

Treatments for early-onset gastric cancer (EOGC) patients are rarely included in clinical trials, resulting in an unclear impact on survival. This study aimed to investigate the treatment patterns of EOGC patients and their impact on survival. Based on the Surveillance, Epidemiology, and End Results database, we conducted a retrospective analysis of 1639 EOGC patients (< 50 years) diagnosed between 2010 and 2018. Patients with larger tumours, distant metastasis, and AJCC TNM stage in IV were prone to receive nonsurgical treatment. Patients treated with surgery alone had a better prognosis than those receiving SROC or SCRT or nonsurgical treatment. However, analyses stratified by histological type, tumour size and TNM stage showed that patients did not benefit more from SROC and SCRT than from surgery alone. Similar results were observed in the stratified Cox regression risk analysis. Patients who received nonsurgical treatment had the highest risk of overall death [hazard ratio (HR) = 2.443, 95% confidence interval (CI) 1.865-3.200, P < 0.001]. This study indicated that additional radiotherapy, chemotherapy or chemoradiotherapy did not provide a coordinated survival benefit to EOGC patients.

The 100 Most-Cited Articles in the Field of Colorectal Diseases from 1955 to 2020: A Bibliometric Analysis.

BACKGROUND: The number of times that an article is cited could reflect its impact. This study aims to recognize and analyze the characteristics of the most frequently cited articles in the field of colorectal diseases. METHODS: We identified the 100 most-cited articles using the terms "colorectal," "colon," "rectal," "IBD," "ulcerative colitis," "Crohn's disease," or "colonoscopy" in Web of Science. The articles were analyzed to evaluate the characteristics, including the number of citations, country of origin, the institution of origin based on the first author's affiliation, study type, and others. RESULTS: Of the top-cited publications, the number of citations ranged from 1575 to 9283, with a mean of 2504.11 citations. The journal with the greatest number of most-cited articles was the New England Journal of Medicine (n = 23), followed by Science (n = 14) and Nature (n = 12). These papers were published in 14 different countries, of which more than half were from the United States (n = 60). The most popular field was colorectal cancer (n = 45), followed by colon tumors (n = 21). Most of the papers were basic science studies (n = 43) and randomized controlled trials (n = 30). Regarding the level of evidence, there were 5 studies at level I, 29 at level II, and 5, 1, and 15 studies at levels III, IV, and V, respectively. CONCLUSION: Our study could provide a historical perspective on scientific progress in the field of colorectal diseases. These 100 mostcited articles are of great significance for helping researchers understand this field over time.

Development and validation of prognostic nomograms for patients with metastatic small bowel adenocarcinoma: a retrospective cohort study.

We aimed to explore factors associated with prognosis in patients with metastatic small bowel adenocarcinoma (SBA) as well as to develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS). Relevant information of patients diagnosed between 2004 and 2016 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms for predicting 1- and 3-year OS and CSS were established with potential risk factors screened from multivariate cox regression analysis. The discrimination and accuracy of the nomograms were assessed by concordance index (C-index), calibration plots, and the area under receiver operating characteristic curve (AUC). In total, 373 SBA patients with M1 category were enrolled. Multivariate analysis revealed that age, size and grade of primary tumor, primary tumor surgery, and chemotherapy were significant variables associated with OS and CSS. The C-index values of the nomogram for OS were 0.715 and 0.687 in the training and validation cohorts, respectively. For CSS, it was 0.711 and 0.690, respectively. Through AUC, decision curve analysis (DCA) and calibration plots, the nomograms displayed satisfactory prognostic predicted ability and clinical application both in the OS and CSS. Our models could be served as a reliable tool for prognostic evaluation of patients with metastatic SBA, which are favorable in facilitating individualized survival predictions and clinical decision-making.

Endoscopic and surgical treatment of T1N0M0 colorectal neuroendocrine tumors: a population-based comparative study.

BACKGROUND: With the rapid advances in endoscopic technology, endoscopic therapy (ET) is increasingly applied to the treatment of small (≤ 20 mm) colorectal neuroendocrine tumors (NETs). However, long-term data comparing ET and surgery for management of T1N0M0 colorectal NETs are lacking. The purpose of this work was to compare overall survival (OS) and cancer-specific survival (CSS) of such patients with ET or surgery. METHODS: Patients with T1N0M0 colorectal NETs were identified within the Surveillance Epidemiology and End Results (SEER) database (2004-2016). Demographics, tumor characteristics, therapeutic methods, and survival were compared. Propensity score matching (PSM) was used 1:3 and among this cohort, Cox proportional hazards regression models were performed to evaluate correlation between treatment and outcomes. RESULTS: Of 4487 patients with T1N0M0 colorectal NETs, 1125 were identified in the matched cohort, among whom 819 (72.8%) underwent ET and 306 (27.2%) underwent surgery. There was no difference in the 5-year and 10-year OS and CSS rates between the 2 treatment modalities. Likewise, analyses stratified by tumor size and site showed that patients did not benefit more from surgery compared with ET. Moreover, multivariate analyses found no significant differences in OS [Hazard Ratio (HR) = 0.857, 95% Confidence Interval (CI): 0.513-1.431, P = 0.555] and CSS (HR = 0.925, 95% CI: 0.282-3.040, P = 0.898) between the 2 groups. Similar results were observed when comparisons were limited to patients with different tumor size and site. CONCLUSIONS: In this population-based study, patients with lesions < 10 mm treated endoscopically had comparable long-term survival compared with those treated surgically, which demonstrates ET as an alternative to surgery in T1N0M0 colorectal NETs of < 10 mm. Further high-quality prospective studies are warranted to comprehensively evaluate the role of ET in patients with tumors 10 to 20 mm.

Primary tumor resection improves survival in patients with multifocal intrahepatic cholangiocarcinoma based on a population study.

The purpose of our study was to evaluate the effect of surgery on the survival and prognosis of patients with multifocal intrahepatic cholangiocarcinoma (ICCA). Patients with multifocal ICCA were selected from the SEER (Surveillance, Epidemiology, and End Results) database between 2010 and 2016. Kaplan-Meier analyses and log-rank tests were used to evaluate the difference in survival between the surgery group and the non-surgery group. We applied the Cox proportional hazards regression model to identify prognostic factors of overall survival (OS) and cancer-specific survival (CSS). In total, 580 patients were enrolled in our study, including 151 patients who underwent surgery and 429 patients who did not. The median survival time of surgical patients was longer than non-surgical patients (OS: 25 months vs. 8 months, p < 0.001; CSS: 40 months vs. 25 months, p < 0.001). Similarly, the 5-year survival rate in the surgery group was significantly higher than those in the non-surgery group (5-year OS rate: 12.91% vs. 0%; p < 0.001; 5-year CSS rate:26.91% vs. 0%; p < 0.001). Multivariate Cox analysis showed that the OS (HR:0.299, 95% CI: 0.229-0.390, p < 0.001) and CSS (HR:0.305, 95% CI:0.222-0.419, p < 0.001) of patients undergoing surgical resection were significantly improved. Meanwhile, after propensity score matching (PSM) of the original data, we come to the same conclusion.

Describing Treatment Patterns for Elderly Patients with Intrahepatic Cholangiocarcinoma and Predicting Prognosis by a Validated Model: A Population-Based Study.

Background: Elderly patients with Intrahepatic Cholangiocarcinoma (ICC) are frequently under-represented in clinical trials, which leads to the unclear management of ICC in elderly patients. This study aimed to describe treatment patterns and establish a reliable nomogram in elderly ICC patients. Methods: Based on the Surveillance, Epidemiology, and End Results (SEER) database, we conducted a retrospective analysis of 1651 elderly patients (≥65 years) diagnosed with ICC between 2004 and 2016. Results: For the whole study population, 29.3% received only chemotherapy, 26.7% no tumor-directed therapy, 19.1% surgery alone, 17.5% radiotherapy, and 7.4% surgery plus chemotherapy. Compared with the age group of 65-74 years, patients aged ≥75 years were less likely to accept treatment. Among patients 66-74 years of age, surgery alone resulted in a median overall survival (OS) of 30 months, surgery combined with chemotherapy 26 months, radiotherapy 17 months, chemotherapy alone 10 months and no therapy 3 months; while among patients ≥75 years of age, the median OS was 21, 25, 14, 9 and 4, respectively. Moreover, independent prognostic indicators including age, gender, grade, tumor size, T stage, N stage, M stage, and treatment were incorporated to construct a nomogram. The C-indexes of the OS nomogram were 0.725 and 0.724 for the training and validation cohorts, respectively. Importantly, the predictive model harbored a better discriminative power than the American Joint Committee on Cancer TNM staging system. Conclusion: Active treatment should not be abandoned among all the elderly patients with ICC. The validated nomogram provided an effective and practical tool to accurately evaluate prognosis and to guide personalized treatment for elderly ICC patients.

Primary Tumor Resection Improves Survival in Patients With Metastatic Gastrointestinal Stromal Tumors: A Preliminary Population-Based Analysis.

Background: Surgery has been the primary treatment in patients with localized gastrointestinal stromal tumors (GISTs) for many decades, whereas it remains controversial regarding the efficacy of primary tumor resection for metastatic GISTs treated with chemotherapy, and likewise it is unclear who would benefit from the surgical resection. Methods: GISTs patients with distant metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of surgery on survival. Results: In total, of 455 patients with metastatic GISTs, 235 patients (51.6%) underwent primary tumor resection and 220 patients (48.4%) did not. Median survival of patients in resection group was 72 (95% CI: 62.90-81.10) months vs. 40 (95% CI: 29.53-50.47) months for those in non-resection group (p < 0.001). Similarly, surgery in conjunction with chemotherapy led to a favorable impact on survival than chemotherapy alone (OS: 72 vs. 40 months, p < 0.001; CSS: 74 vs. 44 months, p < 0.001). Multivariable analysis showed that both OS (HR: 0.581, 95% CI: 0.386-0.874, p = 0.009) and CSS (HR: 0.663, 95% CI: 0.439-0.912, p = 0.042] were dramatically improved in patients with surgical removal of primary site, as well as primary tumor size between 5 and 10 cm, while increasing age was predictive of poorer survival. Stratified analysis revealed that patients with tumor locations in the stomach demonstrated a prolonged survival after surgery, with no significant differential surgical effect between the stomach and small intestine. Conclusions: Our study preliminarily suggests that carefully selected patients with metastatic GISTs might prolong survival after treatment of surgery, especially those with a primary tumor between 5 and 10 cm and a tumor located in the stomach.

Prognostic and clinicopathological significance of SNHG20 in human cancers: a meta-analysis.

BACKGROUND: It has been widely reported that the expression levels of SNHG20 are elevated in diverse types of cancers, indicating that SNHG20 may participate in cancer initiation and development. Besides, accumulating evidence reveals that SNHG20 overexpression is also connected with poor clinical outcomes among cancer patients. Herein, we carry out a systematic meta-analysis to further determine the prognostic and clinical significance of SNHG20 expression in various human cancers. METHODS: Qualifying publications were selected by searching for keywords in PubMed, Embase, Web of Science and Cochrane Library databases, up to September 1, 2019. Pooled hazard ratio (HR) or odds ratio (OR) with corresponding 95% confidence interval (CI) was computed to estimate the strength of association between SNHG20 and survival of cancer patients or clinicopathology using Stata 14.0 software. RESULTS: In total, 15 studies encompassing 1187 patients met the inclusion criteria were ultimately enrolled for analysis. According to the meta-analysis, patients with high SNHG20 expression were markedly linked to poorer overall survival (OS) (pooled HR = 2.47, 95% CI 2.05-2.98, P = 0.000) and disease-free survival/recurrence-free survival/progression-free survival (DFS/RFS/PFS) (pooled HR = 2.37, 95% CI 1.60-3.51, P = 0.000). Additionally, regarding clinicopathology of patients, enhanced SNHG20 was correlated with advanced tumour-node-metastasis (TNM) stage (OR = 2.80, 95% CI 2.00-3.93, P = 0.000), larger tumor size (OR = 3.08, 95% CI 2.11-4.51, P = 0.000), positive lymph nodes metastasis (OR = 2.99, 95% CI 2.08-4.31, P = 0.000), higher tumor stage (OR = 4.51, 95% CI 2.17-9.37, P = 0.000) and worse histological grade (OR = 1.95, 95% CI 1.44-2.63, P = 0.000), but not with gender, smoking status or distant metastasis. CONCLUSIONS: Up-regulated SNHG20 expression is ubiquitous in different kinds of cancers. Moreover, up-regulated SNHG20 expression is capable of serving as an innovative predictive factor of inferior clinical outcomes in cancer patients. Nevertheless, higher-quality multicenter studies are required to corroborate our results.

Long noncoding RNA SNHG6 mainly functions as a competing endogenous RNA in human tumors.

Increased expression of the small nucleolar RNA host gene 6 (SNHG6) has been reported in different cancers, such as hepatocellular carcinoma, colorectal cancer, and lung cancer. The high expression level of SNHG6 is associated with tumor progression and poor prognosis. This paper provides an overview of recent studies on the oncogenic role and potential clinical utilities of SNHG6. Upregulated SNHG6 arrests tumor cell cycle and reduces apoptosis but promotes migration, invasion, metastasis, epithelial-mesenchymal transition (EMT), and chemoresistance in tumors. Mechanically, SNHG6 primarily sponges tumor suppressor microRNA (miRNA), functioning as a competing endogenous RNA. Once sponged, miRNA is unable to degrade, silence, or hamper the translation of its downstream, mostly oncogenic genes, ultimately driving cancer-related processes. Thus, SNHG6 might serve as a biomarker for cancer diagnosis and prognosis.

Comparison of endoscopic versus laparoscopic resection for gastric gastrointestinal stromal tumors: A preliminary meta-analysis.

BACKGROUND AND AIM: For localized disease, complete surgical resection is regarded as the "gold standard" therapeutic modality. With the rapid development of endoscopic techniques, endoscopic resection (ESR) has been confirmed as an efficient and safe alternative for the treatment of gastrointestinal stromal tumors (GISTs) in the stomach. Nevertheless, the management of gastric GISTs remains poorly defined. The purpose of this study is to evaluate the security and effectiveness of ESR with laparoscopic resection (LAR) for gastric GISTs. METHODS: A literature search of online databases was conducted to identify relevant comparative studies of ESR and LAR procedures for gastric GISTs published before April 10, 2020. The cumulative data analysis was also performed utilizing the software STATA. RESULTS: In total, 10 studies involving 1165 patients met the inclusion criteria for analysis (651 for ESR and 514 for LAR). From the results of meta-analysis, patients who underwent ESR experienced decreased operative time (P = 0.000), less intraoperative blood loss (P = 0.002), earlier time to diet (P = 0.000), shorter hospital stay (P = 0.000), and lower total charges (P = 0.000) compared with LAR. Moreover, there were no significant differences between these two approaches concerning tumor rupture, conversion rate to other procedure, complete resection rate, postoperative complication rate, recurrence rate, and disease-free survival. CONCLUSIONS: Endoscopic resection, as an effective alternative treatment strategy with satisfactory outcomes, is acceptable for selective patients with gastric GISTs compared with LAR. Further well-designed randomized controlled trials with large samples are warranted to corroborate our observations.

Prognostic and clinicopathological significance of SNHG6 in human cancers: a meta-analysis.

BACKGROUND: Recently, accumulating evidence has suggested that the aberrant expression of SNHG6 exists in a variety of tumors and has a correlation with poor clinical outcomes across cancer patients. Considering the inconsistent data among published studies, we aim to assess the prognostic effect of SNHG6 on malignancies. METHODS: We retrieved relevant publications in Web of Science, Embase, MEDLINE, PubMed and Cochrane Library based on predefined selection criteria, up to October 1, 2019. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to evaluate the correlation between SNHG6 and overall survival (OS), recurrence-free survival (RFS) and progression-free survival (PFS) as well as clinicopathology. RESULTS: In total, 999 patients from 14 articles were enrolled in our meta-analysis. The results revealed that augmented SNHG6 expression was significantly correlated with poor OS (HR = 2.20, 95% CI = 1.76-2.75, P < 0.001) and RFS (HR = 3.10, 95% CI = 1.90-5.07, P < 0.001), but not with PFS (HR = 2.11, 95% CI = 0.82-5.39, P = 0.120). In addition to lung cancer and ovarian cancer, subgroup analysis showed that the prognostic value of SNHG6 across multiple tumors was constant as the tumor type, sample size, and methods of data extraction changed. Moreover, cancer patients with enhanced SNHG6 expression were prone to advanced TNM stage (OR = 3.31, 95% CI = 2.46-4.45, P < 0.001), distant metastasis (OR = 4.67, 95% CI = 2.98-7.31, P < 0.001), lymph node metastasis (OR = 2.59, 95% CI = 1.41-4.77, P = 0.002) and deep tumor invasion (OR = 3.75, 95% CI = 2.10-6.69, P < 0.001), but not associated with gender, histological grade and tumor size. CONCLUSIONS: SNHG6 may serve as a promising indicator in the prediction of prognosis and clinicopathological features in patients with different kinds of tumors.