Extracellular vesicle biomarkers in circulation for colorectal cancer detection: a systematic review and meta-analysis.

We provided an overview which evaluated the diagnostic performance of circulation EV biomarkers for CRC from PubMed, Medline, and Web of Science until 21 August 2022.Weidentified 48 studies that involved 7727 participants and evaluated 162 plasma/serum individual EV biomarkers including 117 RNAs and 45 proteins, as well as 45 EV biomarker panels for CRC detection. 12 studies evaluated the diagnostic performance of EV biomarkers for early CRC. The summarized sensitivity, specificity, and AUC value of individual EV RNAs and EV RNA panels were 76%, 75%, 0.87 and 82%, 79% and 0.90, respectively. Meanwhile, those of individual EV proteins and EV protein panels were 85%, 84%, 0.92 and 87%, 83%, 0.92, respectively. These results indicated that EV biomarker panels revealed superior diagnostic performance than the corresponding individual biomarkers. In early CRC, EV biomarkers showed available diagnostic value with the sensitivity, specificity, and AUC value of 80%, 75%, and 0.89.In subgroup analyses, EV miRNAs and LncRNAs held similar diagnostic value with the sensitivity, specificity and AUC value of 75%, 78%, 0.90 and 79%, 72%, 0.83, which was highly consistent with the whole EV RNAs. Significantly, the diagnostic values of EV miRNAs in plasma were marginally higher than those based on serum. In detail, the sensitivity, specificity, and AUC values were 79%, 81%, and 0.92 in plasma, as well as 74%, 77%, and 0.88 in serum, respectively. Therefore, circulation EV biomarkers could be considered as a promising biomarker for the early detection of CRC.

CCND2 is a prognostic biomarker and correlates with immune infiltration in lung adenocarcinoma.

Background: CCND2 expression influences the growth and proliferation of cancer cells and plays a crucial role in immune response of tumor. However, few studies focused on the correlation between CCND2 and lung adenocarcinoma (LUAD) in terms of prognosis and tumor immune infiltration. Methods: Original LUAD case data were screened from The Cancer Genome Atlas (TCGA) database. Using R software, we analyzed differently expressed CCND2 between LUAD and adjacent normal tissues. Kaplan-Meier analysis was conducted to determine the relationship between CCND2 expression and the overall survival of LUAD patients, and Cox regression analysis was performed to identify the independently prognostic risk factors for LUAD. Using TIMER (Tumor Immune Estimation Resource) and CIBERSORTx (Cell-type Identification by Estimating Relative Subsets of known RNA Transcripts) databases, the connection between CCND2 expression and LUAD immune infiltration was investigated. Results: The level of CCND2 was significantly lower in LUAD than in adjacent normal tissues [adjusted P<0.05 and log2 fold change (FC) =-1.33]. LUAD patients who expressed lower CCND2 had a shorter overall survival (P=0.046) and CCND2 was an independently prognostic risk factor for LUAD [hazard ratio (HR): 0.77, P=0.049]. In LUAD patients, CCND2 expression was positively associated with the levels of B cells (r=0.159, P=4.00e-04), CD8+ T cells (r=0.287, P=7.88e-11), CD4+ T cells (r=0.301, P=8.14e-12), macrophages (r=0.128, P=4.57e-03), neutrophils (r=0.373, P=1.07e-17), and myeloid dendritic cells (r=0.284, P=1.43e-10). The levels of B cells and macrophages had significantly association with the overall survival of LUAD patients. CIBERSORTx showed that the proportions of naive B cells, resting dendritic cells, and macrophages M1 were higher in the low CCND2 expression group (P<0.05); whereas macrophages M1, activated natural killer (NK) cells, and resting CD4+ memory cells were lower (P<0.05). Conclusions: CCND2 can be exploited as a novel prognostic biomarker involved in immune infiltration of LUAD, hence providing new preventative and therapeutic options for LUAD.

Primary pulmonary monophasic synovial sarcoma initially presenting with bloody pleural effusion: A case report and literature review.

Key Clinical Message: Primary pulmonary synovial sarcoma (PPSS) can originate from blood vessels of the bronchial wall, lung interstitium, and interstitial components, and accounts for 0.1%-0.5% of all primary lung malignancies, the most common symptoms are chest pain, cough, dyspnea, and hemoptysis. Abstract: Synovial sarcoma (SS) is a rare malignant tumor of stromal origin, which accounts for approximately 8%-10% of all soft tissue sarcomas. Primary pulmonary synovial sarcoma (PPSS) can originate from blood vessels of the bronchial wall, lung interstitium, and interstitial components, and accounts for 0.1%-0.5% of all primary lung malignancies. Patient concerns: We report the first case of a 57-year-old man with bloody pleural effusion as an initial manifestation of PPSS in the middle lobe of the right lung diagnosed after surgery. Diagnosis: Chest computed tomography (CT) revealed a mass in the middle lobe of the right lung, which was pathologically diagnosed as a monophasic SS after surgical resection. Interventions: Ten days after preoperative closed chest drainage, a right thoracotomy was performed to remove the right middle lobe of the lung. Outcomes: The patient recovered smoothly and was discharged from the hospital without any other postoperative treatment. A follow-up chest CT scan 7 months postoperatively revealed intrapulmonary recurrence with multiple metastases. Lessons: Monophasic PPSS of the lung may present with bloody pleural effusion as its first manifestation.

Extracellular vesicle biomarkers in circulation for the diagnosis of gastric cancer: A systematic review and meta­analysis.

The prognosis of a gastric cancer (GC) diagnosis is poor due to the current lack of effective early diagnostic methods. Extracellular vesicle (EV) biomarkers have previously demonstrated strong diagnostic efficiency for certain types of cancer, including pancreatic and lung cancer. The present review aimed to summarize the diagnostic value of circulating EV biomarkers for early stage GC. The PubMed, Medline and Web of Science databases were searched from May 1983 to September 18, 2022. All studies that reported the diagnostic performance of EV biomarkers for GC were included for analysis. Overall, 27 studies were selected containing 2,831 patients with GC and 2,117 controls. A total of 58 EV RNAs were reported in 26 studies, including 39 microRNAs (miRNAs), 10 long non-coding RNAs (lncRNAs), five circular RNAs, three PIWI-interacting RNAs and one mRNA, in addition to one protein in the remaining study. Meta-analysis of the aforementioned studies demonstrated that the pooled sensitivity, specificity and AUC value of the total RNAs were 84, 67% and 0.822, respectively. The diagnostic values of miRNAs were consistent with the total RNA, as the pooled sensitivity, specificity and AUC value were 84, 67% and 0.808, respectively. The pooled sensitivity, specificity and AUC values of lncRNAs were 89, 69% and 0.872, respectively, markedly higher compared with that of miRNAs. A total of five studies reported the diagnostic performance of EV RNA panels for early stage GC and reported powerful diagnostic values with a pooled sensitivity, specificity and AUC value of 80, 77% and 0.879, respectively. Circulating EV RNAs could have the potential to be used in the future as effective, noninvasive biomarkers for early GC diagnosis. Further research in this field is necessary to translate these findings into clinical practice.

Extracellular vesicle biomarkers for pancreatic cancer diagnosis: a systematic review and meta-analysis.

BACKGROUND: Extracellular vesicle (EV) biomarkers have promising diagnosis and screening capacity for several cancers, but the diagnostic value for pancreatic cancer (PC) is controversial. The aim of our study was to review the diagnostic performance of EV biomarkers for PC. METHODS: We performed a systematic review of PubMed, Medline, and Web Of Science databases from inception to 18 Feb 2022. We identified studies reporting the diagnostic performance of EV biomarkers for PC and summarized the information of sensitivity, specificity, area under the curve (AUC), or receiver operator characteristic (ROC) curve) in according to a pre-designed data collection form. Pooled sensitivity and specificity was calculated using a random-effect model. RESULTS: We identified 39 studies, including 2037 PC patients and 1632 noncancerous, seven of which were conducted independent validation tests. Seventeen studies emphasized on EV RNAs, sixteen on EV proteins, and sixteen on biomarker panels. MiR-10b, miR-21, and GPC1 were the most frequently reported RNA and protein for PC diagnosis. For individual RNAs and proteins, the pooled sensitivity and specificity were 79% (95% CI: 77-81%) and 87% (95% CI: 85-89%), 72% (95% CI: 69-74%) and 77% (95% CI: 74-80%), respectively. the pooled sensitivity and specificity of EV RNA combined with protein panels were 84% (95% CI: 81-86%) and 89% (95% CI: 86-91%), respectively. Surprisingly, for early stage (stage I and II) PC EV biomarkers showed excellent diagnostic performance with the sensitivity of 90% (95% CI: 87-93%) and the specificity of 94% (95% CI: 92-95%). Both in sensitivity and subgroup analyses, we did not observe notable difference in pooled sensitivity and specificity. Studies might be limited by the isolation and detection techniques of EVs to a certain extent. CONCLUSIONS: EV biomarkers showed appealing diagnostic preference for PC, especially for early stage PC. Solving the deficiency of technologies of isolation and detection EVs has important implications for application these novel noninvasive biomarkers in clinical practice.

Construction and validation of a novel prognostic model for lung squamous cell cancer based on N6-methyladenosine-related genes.

BACKGROUND: N6-methyladenosine (m6A) is the most prevalent modification in mRNA in biological processes and associated with various malignant tumor initiation and progression. The present study aimed to construct a prognostic risk model based on m6A-related genes (the downstream genes influenced by m6A modulators) for LUSC. METHODS: Based on TCGA, we stratified LUSC patients with and without genetic alteration of m6A modulators into altered and unaltered groups. Using univariate Cox and Lasso regression analyses, we identified prognostic m6A-related genes to construct a prognostic risk model. We then applied a multivariate Cox proportional regression model and the survival analysis to evaluate the risk model. Moreover, we performed the Receiver operating characteristic curve to assess the efficiency of the prognostic model based on TCGA and GSE43131. We analyzed the characteristics of tumor-associated immune cell infiltration in LUSC through the CIBERSORT method. RESULTS: Three m6A-related genes (FAM71F1, MT1E, and MYEOV) were identified as prognostic genes for LUSC. A novel prognostic risk model based on the three m6A-related genes was constructed. The multivariate Cox analysis showed that the prognostic risk model was an independent risk factor (HR = 2.44, 95% CI = 1.21~3.56, p = 0.029). Patients with a high-risk group had worse overall survival both in TCGA (p = 0.018) and GSE43131 (p = 0.00017). The 1, 2, and 3-year AUC value in TCGA was 0.662, 0.662, and 0.655, respectively; The 1, 2, and 3-year AUC value in GSE43131 was 0.724, 0.724, and 0.722, respectively. The proportion of infiltrated neutrophils in the high-risk group was higher than that in the low-risk group (p = 0.028), whereas that of resting NK cells (p = 0.002) was lower. CONCLUSION: A novel prognostic risk model based on three m6A-related genes for LUSC was generated in this study.

Achieving NIR Light-Mediated Tumor-Specific Fenton Reaction-Assisted Oncotherapy by Using Magnetic Nanoclusters.

As an emerging strategy for oncotherapy, Fenton chemistry can efficiently improve the conversion from endogenous H2O2 into highly toxic ·OH in the whole high-performance therapeutic process. Although promising, the efficiency of Fenton reaction in tumor regions is highly limited by the inefficient delivery of Fenton reagents and the restrictive conditions of tumor microenvironment. One promising strategy against the above limitations is to specifically increase the temperature around the tumor regions. In this study, a novel NIR light-mediated tumor-specific nanoplatform based on magnetic iron oxide nanoclusters (MNCs) was rationally designed and well developed for photothermally enhanced Fenton reaction-assisted oncotherapy. MNCs could accumulate into the tumor regions with the help of an external magnet field to enable T2-weighted magnetic resonance (MR) imaging of tumors and MR imaging-guided combined antitumor therapy. Our well-prepared MNCs also revealed excellent photothermal effect upon a NIR light irradiation, promising their further important role as a photothermal therapy (PTT) agent. More importantly, heat induced by the PTT of MNCs could accelerate the release of Fe from MNCs and enhance the efficiency of Fenton reaction under H2O2-enriched acidic tumor microenvironment. Results based on long-term toxicity investigations demonstrated the overall safety of MNCs after intravenous injection. This work therefore introduced a novel nanoplatform based on MNCs that exerted a great antitumor effect via photothermally enhanced tumor-specific Fenton chemistry.

Identification of prognostic miRNA biomarkers for esophageal cancer based on The Cancer Genome Atlas and Gene Expression Omnibus.

ABSTRACT: MicroRNAs (miRNAs) in tumor and tumor-adjacent tissues can be effective diagnostic and prognostic markers to monitor tumor occurrence and progression. Despite improvements in the diagnosis and treatment of esophageal cancer (EC), the survival rate is <25%; consequently, more effective EC-specific prognostic biomarkers are urgently needed to design effective treatment regimens. In this study, we focused on identifying independent prognostic miRNA signatures in tumor and tumor-adjacent tissues in EC.We screened candidate miRNAs using a genome-wide miRNA transcriptome dataset from The Cancer Genome Atlas (TCGA) database that included 82 patients with esophageal adenocarcinoma (EADC) and 83 patients with esophageal squamous cell carcinoma (ESCC). We validated potential prognostic miRNA markers using a microarray profiling dataset that included information of 32 patients with EADC and 44 patients with ESCC from the Gene Expression Omnibus database. TCGA dataset was additionally used to identify differentially expressed mRNAs (DEMs) between the tumor and tumor-adjacent tissues. Univariate and multivariate Cox analyses were performed to detect the relationship between miRNAs and the overall survival of patients with EC. Kaplan-Meier method was applied to assess the survival differences between groups with differential miRNA expression. Lastly, functional enrichment analysis was conducted using miRWalk 2.0 online database for annotation.Although there was a considerable difference between the DEMs of EADC and ESCC, 73 DEMs were differentially expressed in both EADC and ESCC samples in TCGA dataset. Cox regression and Kaplan-Meier survival analyses showed that a higher expression of hsa-miR-186-5p and hsa-let-7d-5p was independently associated with a poor prognosis of EADC and ESCC, respectively. Furthermore, gene functional enrichment analysis revealed that the target genes of hsa-miR-186-5p and hsa-let-7d-5p participated in various cancer-related pathways, including the MAPK signaling pathway, proteoglycans in cancer, and AGE-RAGE signaling pathway.Our results revealed that hsa-miR-186-5p and hsa-let-7d-5p could be used as independent prognostic biomarkers for EADC and ESCC, respectively.

Rotating night shift work is associated with an increased risk of gastroesophageal reflux disease (GERD) symptoms among workers in China: A cross-sectional study.

AIMS OF THE STUDY: Increasing studies suggest a significant association between night shift work and an increased risk of type 2 diabetes, obesity and other metabolic disorders. However, the available evidence of the association of rotating night shift work with gastroesophageal reflux disease (GERD) is limited. Herein, we hypothesised a link between the GERD risk and rotating night shift work among workers in China. METHODS USED TO CONDUCT THE STUDY: A total of 2027 workers who completed a comprehensive health checkup were included. Logistic regression was used to investigate the link between rotating night shift work and the risk of GERD symptoms. Receiver operating characteristic (ROC) curve analysis was used to assess the multivariable model's diagnostic value for identifying GERD symptoms among workers. RESULTS OF THE STUDY: In total, 556 (27.4%) individuals had GERD symptoms among 2027 workers. Multivariate analysis showed five independent factors for GERD: rotating night shift work (OR = 3.66, 95% CI: 2.52-5.40), age (OR = 2.53, 95% CI: 1.67-3.78), smoking (OR = 3.70, 95% CI: 2.63-5.21), Helicobacter pylori (H. pylori) infection (OR = 0.68, 95% CI: 0.48-0.96) and obesity (OR = 3.04, 95% CI: 2.43-3.83). A five-variable model based on five independent factors provided an area under a ROC curve (AUROC) of 0.80 (95% CI: 0.78-0.81) for identifying GERD symptoms among workers. CONCLUSIONS DRAWN FROM THE STUDY AND CLINICAL IMPLICATIONS: Rotating night shift work is independently associated with an increased risk of GERD symptoms. Moreover a five-variable model (rotating night shift work, age, smoking, H pyori infection and obesity) can help identify individuals at high risk for GERD symptoms among workers in China.

The clinical and prognostic impact of aldehyde dehydrogenase 1 in non-small cell lung cancer: a meta-analysis.

BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) has been identified as a cancer stem cell marker. However, the clinical role of ALDH1 in non-small cell lung cancer (NSCLC) remains conflicting. This study was conducted to investigate the correlation of ALDH1 with NSCLC patients' clinicopathological characteristics and prognosis. METHODS: The electronic databases were searched for the available literature. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) or hazard ratios (HRs: multivariate Cox analysis) with 95% CIs were used to evaluate the impact of ALDH1 on NSCLC. RESULTS: Final 13 eligible studies with 2,407 patients published between 2009 and 2019 were identified. ALDH1 expression was not correlated with age, gender, smoking behavior, clinical stage, histological grade, lymph node metastasis, and distal metastasis, but the results demonstrated a positive association of ALDH1 expression with recurrence (yes vs. no: OR =2.82, 95% CI, 1.17-6.80, P=0.021) and a negative association of ALDH1 expression with vascular invasion (positive vs. negative: OR =0.63, 95% CI, 0.41-0.98, P=0.04). ALDH1 expression was significantly lower in adenocarcinoma (AD) than in squamous cell carcinoma (SCC) (OR =0.39, 95% CI, 0.30-0.51, P<0.001). Multivariate Cox analysis showed that ALDH1 expression was not associated with overall survival (OS) and disease-free survival (DFS), but was correlated with improved disease-specific survival (DSS) (HR =0.47, 95% CI, 0.22-0.98, P=0.043). CONCLUSIONS: ALDH1 expression may be an independent favorable prognostic marker for DSS in NSCLC.

Circulating miR-17 as a promising diagnostic biomarker for lung adenocarcinoma: evidence from the Gene Expression Omnibus.

BACKGROUND: A definitive preoperative diagnosis of lung adenocarcinoma (LUAD) is a clinical challenge. Informative and blood-based microRNAs (miRNAs) may provide new insights on LUAD screening and detection but are limited by suboptimal accuracy. METHODS: The raw expression levels of circulating miR-21, miR-155, miR-210, miR-126, miR-182, and miR-17 in LUAD cases and healthy controls from the Gene Expression Omnibus (GEO) database were obtained and analyzed to identify accurate diagnostic miRNAs biomarkers for LUAD detection. We applied a meta-analysis to determine the magnitude of statistically significant miRNAs in LUAD samples, based on estimation outcomes acquired by analyzing raw data. Furthermore, bioinformatics analysis was conducted to reveal the function of significant miRNAs in the comprehensive underlying mechanisms of LUAD biology. RESULTS: A total of 5 raw microarray datasets, including 87 LUAD samples and 83 healthy controls, were eligible. Through our analysis, the primary outcome measure was that circulating miR-17 showed a favorable accuracy in diagnosing LUAD, and the overall pooled area under the curve (AUC) value was 0.79. Furthermore, a total of 85 predicted target genes were chosen, and 29 gene ontology (GO) items and 3 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed a significant statistical difference, which demonstrated that the target genes are involved in the biological processes of LUAD. A protein-protein interaction (PPI) network analysis revealed 10 hub genes, namely CCND2, E2F3, TNRC6B, AGO1, AAK1, RAB5B, LDLR, FBXO21, UBE3C, and MYLIP, located in the center of the PPI network. CONCLUSIONS: In conclusion, circulating miR-17 may be a quality diagnostic biomarker for LUAD screening, but confirmation by a large, rigorous clinical validation in a longitudinal setting is warranted.

Circulating microRNAs as promising diagnostic biomarkers for pancreatic cancer: a systematic review.

Pancreatic cancer (PC) is one of the most common forms of malignant tumors and causes of tumor-related death worldwide. The current prognosis of PC still remains poor due to the lack of effective early detection method. Recently, there is strong support that circulating miRNAs can be used as biomarkers for early detection of various cancers, including PC. The purpose of this review is to provide an overview of previous published studies on circulating miRNAs in plasma/serum for early detection of PC and summarize their diagnostic value. PubMed, Embase and Web of Science were systematically searched for eligible studies on circulating miRNAs for PC detection. Overall, 29 studies published between 2009 and 2018 evaluating 51 individual miRNAs (no P-value exceeding 0.05) and 13 miRNAs panels were included. Generally, the diagnostic performance of circulating miRNAs for PC detection was strong, with both the sensitivity and specificity of 36% individual miRNAs and 40% miRNAs panels exceeding 80%. Moreover, two promising miRNA panels were discovered and verified externally with all AUC values exceeding 0.95. Therefore, circulating miRNAs may hold potential to be used as noninvasive diagnostic biomarkers for PC, but large-scale studies are still needed to validate the promising miRNAs and optimize the miRNA panels. Since, the tremendous heterogeneity of studies in this field hampers translating miRNA markers into clinical practice, miRNA analytical procedures are also needed to be standardized in the future.

Nonalcoholic fatty liver disease increases the risk of gastroesophageal reflux disease: A systematic review and meta-analysis.

BACKGROUND: Increasing evidence indicates that nonalcoholic fatty liver disease (NAFLD) is linked to an increased risk of extra-hepatic conditions. However, it is currently uncertain whether NAFLD is associated with the risk of gastroesophageal reflux disease (GERD). We performed a systematic review and meta-analysis of relevant studies to examine the association between NAFLD and the risk of GERD. METHODS: We searched PubMed, Scopus, Embase and Web of Science from 1 January 1975 to 15 December 2018, using predefined terms to identify cross-sectional, case-control and cohort studies investigating the association between NAFLD and GERD. RESULTS: Nine observational studies involving 185 118 subjects were eligible for inclusion in the meta-analysis. Overall, NAFLD was significantly associated with an increased risk of GERD (random effect OR 1.28; 95% CI: 1.12-1.44, I2  = 82%). Moreover, the significant association between NAFLD and GERD was consistent both for studies with adjusted OR/HR (n = 6, random effect OR = 1.16, 95% CI: 1.03-1.30) and those with unadjusted OR/HR (n = 3, random effect OR = 2.09, 95% CI: 1.62-2.56) as measures of effect. Both funnel plot and Egger's test suggested the existence of publication bias. However, a sensitivity analysis by sequentially omitting each study did not alter the pooled outcome,suggesting the robustness of the association. CONCLUSION: NAFLD is associated with an increased risk of GERD. However, future large and cohort studies are still needed to determine the causal relationship between NAFLD and the risk of GERD.

Advantages of 99mTc-3PRGD2 SPECT over CT in the preoperative assessment of lymph node metastasis in patients with esophageal cancer.

BACKGROUND: Our study was designed to compare the diagnostic efficacies of integrated 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single-photon emission computed tomography (SPECT) images and computed tomography (CT) images in lymph node metastasis in the patients with esophageal cancer. METHODS: From September 2015 and May 2018, 32 patients with histologically proven primary esophageal carcinoma underwent both 99mTc-3PRGD2 SPECT and CT scans followed by esophagectomy with lymph node dissection. The results of reviewing 99mTc-3PRGD2 SPECT and CT images for the lymph node metastasis were compared in relation with pathologic findings. RESULTS: During surgery, a total of 168 lymph nodes were dissected in 32 patients, of which 42 node groups in 18 patients were malignant on histologic examination. Preoperative nodal staging was compared with postoperative histopathological staging, The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 99mTc-3PRGD2 SPECT for lymph nodes were 80.95%, 86.51%, 85.12%, 66.67%, and 93.16% on per-node basis, respectively; compared with 59.52%, 73.02%, 69.64%, 42.37%, and 84.40% for CT (p = 0.034, 0.008, 0.005, 0.011, and 0.038, respectively). 70.59% (12/17) false-negative interpretations and 50% (17/34) false-positive interpretations on CT were corrected by 99mTc-3PRGD2 SPECT. 37.5% false-negative interpretations on 99mTc-3PRGD2 SPECT were corrected by CT. 11.90% (5/42) positive lymph nodes and 13.49% (17/126) negative nodes at pathology were incorrectly diagnosed both by 99mTc-3PRGD2 SPECT and CT. The accuracy of 99mTc-3PRGD2 SPECT (87.50%, 28/32) was significantly higher than that of CT (62.50, 20/32; p = 0.022) on per-patient basis. 99mTc-3PRGD2 SPECT showed significantly higher sensitivity and accuracy in the neck and upper thoracic regions than CT. For nodal staging, 99mTc-3PRGD2 SPECT was correct in 78.12% (25/32) of the patients, whereas CT was correct in 53.12% (17/32), p = 0.037. CONCLUSION: 99mTc-3PRGD2 SPECT is more accurate than CT for preoperative assessment of lymph node metastasis in esophageal cancer and may be helpful in determining the therapeutic plan.

Blockade of CCL2 enhances immunotherapeutic effect of anti-PD1 in lung cancer.

Myeloid derived suppressor cells (MDSC) play a pivotal role in tumor immune evasion and MDSC levels increased in patients with cancer. Studies confirmed the associations between MDSC and various cytokines in the peripheral blood. However, little is known about the association between parenchymal MDSC subsets and cytokines, or the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and CCL2 level in lung cancer model. G-MDSC and M-MDSC from the blood and parenchyma were analyzed by flow cytometry and western blot in the lung tumor model. CCL2 was detected by ELISA assay, real-time PCR, western blot and flow cytometry. Furthermore, the therapeutic effects of combination treatment combining CCL2 antagonist and anti-PD1 antibody were assessed. Results showed that MDSC subsets had a positive correlation with CCL2, suggesting CCL2 may attract MDSC into the parenchyma. Gene and protein expression of CCL2, as well as the CCL2 surface expression significantly increased in blood and tumor of tumor-bearing mice. Anti-CCL2 treatment decreased G-MDSC and M-MDSC in the periphery and tumor through inhibiting the protein expression of arginase 1 and iNOS. In addition, combination therapy enhanced CD4+ and CD8+ T cell infiltration, as well as the production of interferon gamma (IFNγ), and increased the survival time of tumor-bearing mice. Our study provided potential new target to enhance the efficacy of immunotherapy in patients with lung cancer, in addition to elucidate a possible association between MDSC subsets and the cytokine drawing MDSC migration into the tumor tissue.

Esophageal hiatal hernia: risk, diagnosis and management.

INTRODUCTION: Esophageal hiatal hernia involves abnormal abdominal entry into thoracic cavity. It is classified based on orientation between esophageal junction and diaphragm. Sliding hiatal hernia (Type-I) comprises the most frequent category, emanating from right crus of diaphragm. Type-II esophageal hernia engages both left and right muscular crura. Type-III and IV additionally include the left crus. Age and increased body mass index are key risk factors, and congenital skeletal aberrations trigger pathogenesis through intestinal malrotations. Familiar manifestations include gastric reflux, nausea, bloating, chest and epigastric discomfort, pharyngeal and esophageal expulsion and dysphagia. Weight loss and colorectal bleeding are severe symptoms. Areas covered: This review summarizes updated evidence of pathophysiology, risk factors, diagnosis and management of hiatal hernias. Laparoscopy and oesophagectomy procedures have been discussed as surgical procedures. Expert commentary: Endoscopy identifies untreatable gastric reflux; radiology is better for pre-operative assessments; manometry measures esophageal peristalsis, and CT scanning detects gastric volvulus and associated organ ruptures. Gastric reflux disease is mitigated using antacids and proton pump and histamine-2-receptor blockers. Severe abdominal penetration into chest cavity demands surgical approaches. Hence, esophagectomy has chances of post-operative morbidity, while minimally invasive laparoscopy entails fewer postoperative difficulties and better visualization of hernia and related vascular damages.

Recurrence in unicentric castleman's disease postoperatively: a case report and literature review.

BACKGROUND: Our case describe a rare recurrence case of Unicentric Castleman's disease (UCD) with hyaline vascular type 14 years after surgery. CASE PRESENTATION: A 35-year-old Chinese female was admitted to hospital with one and half months history chest distress and chest pain. Patient reports a history of thoracic operation for mediastinal mass 14 years ago, and it was diagnosed UCD with hyaline vascular type after postoperative pathological examination. At this time, the imaging examination showed a mediastinal mass once again. Combining the medical history, postoperative microscopically examination and immunoperoxidase staining, patient was again diagnosed UCD with hyaline vascular type again. The hyaline vascular type is the most common type and usually presents as a UCD. Most patients with UCD have no clinical symptoms. The diagnosis of UCD is generally achieved with histological and immunohidtochemical findings postoperatively. Currently, the standard treatment of UCD is the complete surgical resection, with almost no relapse postoperative. The recurrence in UCD with hyaline vascular type postoperative have not previously been reported. Therefore, herein we describe a recurrence case of UCD with hyaline vascular type 14 years after surgery. CONCLUSION: Our case is the first case which reports the relapse of UCD with hyaline vascular type after completely surgery. It indicates that long term follow-up is necessary for patient who is diagnosed UCD after surgery.

Clinical significance of joint detection of serum CEA, SCCA, and bFGF in the diagnosis of lung cancer.

Lung cancer is a type of malignant tumor with highest morbidity and mortality. This study tested three tumor marker levels including CEA, SCCA, and bFGF to explore their value in lung cancer diagnosis and pathological type judgment. Venous blood was extracted from lung cancer patients, lung benign lesion patients and healthy control. Electrochemiluminescence immunoassay was applied to detect serum CEA and SCCA content. ELISA was used to test serum bFGF level. Serum CEA, SCCA, and bFGF levels and positive rates were significantly higher in lung cancer group than that of lung benign disease group and health control (P < 0.05). bFGF showed higher detection sensitivity than CEA in lung cancer (P < 0.05). Three joint detection sensitivity was higher than single test (P < 0.05), while its specificity was lower (P < 0.05), and the accuracy presented no significant difference. Serum CEA and SCCA levels and positive rates were obviously higher in non-small cell lung cancer patients when compared with small cell lung cancer patients (P < 0.05), while bFGF level was similar between small cell lung cancer and non-small cell lung cancer. bFGF showed higher detection rate than SCCA in small cell lung cancer (P < 0.05). Three joint detection exhibited higher positive rate in small cell lung cancer and non-small lung cancer than single test. Serum CEA, SCCA and bFGF joint detection improved detection sensitivity in lung cancer and had important reference value for pathological type deduction.

Non-Epstein-Barr virus-associated double primary lymphoepithelioma-like carcinoma of the esophagus and stomach: a case report and literature review.

A 55-year-old Chinese male was admitted to the hospital for epigastralgia and dysphagia with a two month history, and hematemesis and melena with a two-day history. Two lesions were found in the esophagus and stomach by esophago--gastroduodenoscopy and computed tomography. The patient underwent subtotal esophagectomy and gastrectomy, esophagogastric anastomosis above the aortic arch, and thoracic-abdominal two-field lymph node dissection. Pathological and immumohistochemical studies showed that both lesions had the same form of poorly differentiated carcinoma with dense lymphoid stroma, which was diagnosed as lymphoepithelioma-like carcinoma (LELC). No metastatic relationship was found between the two tumors. Therefore, the case was double primary lymphoepithelioma-like carcinoma of the esophagus and stomach. Epstein-Barr virus (EBV) in the two tumors were negative by EBV-encoded small RNA1 (EBER-1) in situ hybridization. No adjuvant therapy was performed due to his poor physical condition post-operatively, and no evidence of tumor recurrence or metastasis was found during the next 14 months of follow-up. Esophageal and gastric LELC are rare, especially the former, which has a specific geographical distribution. Literature reported cases showed upper gastrointestinal LELC were highly malignant with good prognosis, and EBV was detected less in esophageal LELC cases but more commonly in gastric LELC cases. Upper gastrointestinal LELC lesions are usually singular, and no synchronous lesions were reported in the literature. Our case is the first LELC to present as double primary lymphoepithelioma- like carcinoma of both esophagus and stomach simultaneously, which demonstrates that LELC can be multifocal in the upper gastrointestinal tract.

The association between NFKB1-94ins/del ATTG polymorphism and non-small cell lung cancer risk in a Chinese Han population.

This study aimed to clarify the influence of a common insertion/deletion polymorphism (-94ins/del ATTG, rs28362491) in the Nuclear factor-κB1 (NFKB1) promoter on non-small cell lung cancer (NSCLC) susceptibility. We genotyped the NFKB1 -94ins/del ATTG polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and assessed the association with NSCLC risk, clinicopathological parameters in a case-control study of 421 cases and 425 controls. Heterozygous (ID) genotype disclosed a statistically significantly increased risk of developing NSCLC (OR = 1.57, 95% CI 1.13-2.19, P = 0.007). Homozygous (II) genotype also showed an increased risk of NSCLC (OR = 1.87, 95% CI 1.27-2.75, P = 0.001). Statistically significant difference was observed when the patients and controls were compared according to ID + II versus DD (OR = 2.01, 95% CI 1.47-2.76, P<0.001). The I allele was significantly higher in the NSCLC cases compared to the controls (52.9% versus 45.1%). The I allele was significantly associated with NSCLC risk (OR = 1.37, 95% CI 1.12-1.65, P = 0.001). There was a significantly higher frequency of ID + II genotypes observed in smokers, compared to non-smokers (OR = 1.99, 95% CI 1.22-3.24, P = 0.005) and in patients with stage III + IV, compared to stage I + II (OR = 2.16, 95% CI 1.34-3.49, P = 0.002). This study suggested that NFKB1 -94ins/del ATTG polymorphism was significantly associated with NSCLC risk in Chinese Han population.