VEGF gene rs3025039C/T and rs833052C/A variants are associated with bladder cancer risk in Asian descendants.

INTRODUCTION: Polymorphisms of vascular endothelial growth factor (VEGF) gene were evaluated in a number of studies to evaluate bladder cancer (BCa) susceptibility but with controversial conclusions. MATERIAL AND METHODS: We performed a pooled analysis and used odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) to investigate the correlation between VEGF gene rs3025039C/T and rs833052C/A variants and risk of BCa. Furthermore, we utilized in silico tools to demonstrate the relationship of VEGF expression correlated with BCa susceptibility and survival time. RESULTS: A total of eight studies including 4359 BCa patients and 5417 control subjects were enrolled in our study. For VEGF rs3025039C/T, a significant association was indicated between this variant and BCa risk in homozygote comparison (OR = 1.51; 95% CI = 1.13-2.02; P heterogeneity = 0.815) and recessive genetic model (OR = 1.49; 95% CI = 1.12-1.99; P heterogeneity = 0.874), in particular in an Asian population subgroup. For VEGF rs833052C/A, we observed a positive association between this variant and BCa susceptibility in Asian descendants. Results from in silico tool showed evidence that VEGF expression in bladder carcinoma tissue is higher than that in normal counterpart (transcripts per kilobase million = 7.21 vs 6.85; P < 0.05). CONCLUSIONS: The VEGF gene rs3025039C/T and rs833052C/A variants may contribute to the risk of developing BCa, especially in Asian descendants. Future larger sample studies should be continued to focus on this issue in more detail.

Application of Y-shaped, coated self-expandable metallic stents for anastomotic stenosis after gastrojejunostomy (Billroth II).

BACKGROUND: Anastomotic stenosis is an infrequent but life-threatening complication after gastrojejunostomy (Billroth II). Tubular or single tubular stents have limited efficacy due to the particular anatomy. PURPOSE: To assess the feasibility of a Y-shaped, fully-coated, self-expandable, metallic stent (SEMS) for anastomotic stenosis after gastrojejunostomy (Billroth II). MATERIAL AND METHODS: Between January 2008 and August 2014, 14 patients (10 with gastric carcinoma and four with duodenal ulcers) had anastomotic stenoses following Billroth II reconstructions. Eight patients with gastric cancer had tumor recurrence near the anastomosis; two had benign strictures. The four duodenal ulcer patients had benign stenoses. An integrated Y-shaped, fully coated SEMS was designed to accord with the anatomy of residual gastrojejunal anastomotic strictures. Fourteen stents were inserted under fluoroscopic control. Follow-up was at 1, 3, 9, and 12 months, and then annually. RESULTS: All 14 stents were inserted successfully at the first attempt with a technical success rate of 100%. After stenting, abdominal symptoms resolved in all patients. All patients were followed up for 4-27 months (mean, 13.9 months). One of the eight recurrent cases died of multiple tumor metastases and liver failure after 7 months, without obstruction symptoms. In all six patients with benign anastomotic stenosis, the stents were removed successfully without complication and with no evidence of restenosis based on clinical evaluation and imaging. CONCLUSION: A Y-shaped, fully-coated SEMS proved to be a feasible and minimally invasive procedure for treating anastomotic stenosis after gastrojejunostomy (Billroth II).

Combined T/Y biliary stent placement for the treatment of biliary obstruction caused by Bismuth-Corlett type IV hilar cholangiocarcinoma.

BACKGROUND/AIMS: To assess the feasibility and efficacy of combined T/Y biliary stent for the bilateral drainage of biliary obstruction caused by Bismuth-Corlett type IV hilar cholangiocarcinoma. METHODOLOGY: Eleven patients with unresectable malignant hilar biliary obstruction of Bismuth-Corlett type IV underwent placement of combined T/Y biliary stent. After unilateral or bilateral percutaneous transhepatic cholangiography, "T" or "Y" type combined biliary metal stents were placed based on the intersection angle of the left and right intrahepatic bile ducts. RESULTS: Technical success of stent placement was achieved for all 11 cases. Eight patients had "T" type and three cases had "Y" type stents placement. Internal drainage achieved with no major complications developed, except for minor hemorrhage occurred for two patients (18.2%). The survival time, liver function including bilirubin concentration and degree of dilation of the bile duct improved. CONCLUSIONS: The combined T/Y biliary stent may be feasible and effective for bilaterally drainage of malignant hilar biliary obstruction, this operation is easy to perform, less invasive and shows a good effect of biliary drainage.

Right bronchopleural fistula treated with a novel, Y-shaped, single-plugged, covered, metallic airway stent.

BACKGROUND: Bronchopleural fistula (BPF) is an infrequent but life-threatening complication after pneumonectomy. The incidence of BPF reported in the literature varies from 0.3% to 20%. PURPOSE: To determine the feasibility and efficacy of using Y-shaped, single-plugged, covered, metallic stents to treat right bronchopleural fistulas. MATERIAL AND METHODS: We have designed a Y-shaped, single-plugged, covered, self-expandable, metallic airway stent to fit the specific anatomy of the right main bronchus. The stent has a main tube and two branches, resembling an inverted "Y". One of the branches is closed (plugged) and bullet-shaped; the other one tubular and open. The entire stent is encased in a nitinol wire mesh. Stent size can be individualized using multislice spiral computed tomography (MSCT) measurements of the airways. Under fluoroscopic guidance, we have implanted 15 Y-shaped stents in 15 patients with right bronchopleural fistulas. RESULTS: Stent insertion was successful in all patients. All fistulas were successfully closed immediately after stent placement. Follow-up was performed for 1-34 months. Positive clinical outcomes were seen in 13 of 15 patients. Two patients died of intractable pulmonary infection and multiorgan failure. The fistula completely healed and the stent could be removed in five patients; however, two of them were left with a small, aseptic, residual right lung cavity. The remaining eight patients are still alive with the stent in situ. CONCLUSION: The placement of Y-shaped, single-plugged, covered, self-expandable metallic airway stents seems to be a feasible and safe method for the treatment of bronchopleural fistulas involving the right main bronchus. This stent is a promising therapeutic alternative for bronchopleural fistulas involving the right main bronchus.

Clinical evaluation the success rate and complications of fluoroscopically guided removal of tracheal tube metallic stents.

BACKGROUND: Long-term placement of airway stents has a high probability of restenosis of the airway due to granulation tissue hyperplasia, and it is difficult to remove the stent. Our aim is to evaluate the success rate and complications of removal of tracheal tube metallic stents under fluoroscopic guidance, and to compare the difference between uncovered stent and covered stent. METHODS: We retrospectively reviewed 45 cases (31 males and 14 females; age, 12-71 years) of tracheal metallic stent removal performed at our center between January 2014 and December 2019. Covered stents were applied in 36 cases, and uncovered stents were applied in 9 cases. In the covered stent group, 15 patients presented with granulation tissue at both ends; 3 cases, with stent fracture; and 2, with stent intolerance due to severe airway foreign body sensation. In the uncovered stents group, all patients presented with granulation tissue formation; 2 patients, with stent fracture; and 1 patient, with stent intolerance. RESULTS: A total of 41 (91.1%) stents were successfully removed (34 [94.4%] in the covered stent group and 7 [77.8%] in the uncovered stent group). The average duration of stent placement was 3.2 ± 0.7 and 2.5 ± 1.2 months in the covered stent group and uncovered stent group, respectively. With regard to the complications, hemoptysis occurred in 4 cases (average blood volume lost, 100 ml), tracheal mucosa tear occurred in 5 cases, tracheal collapse requiring emergency airway stent placement occurred in 1 case, and tracheal rupture requiring emergency surgical suture occurred in 1 case. No procedure-related deaths occurred in either group. CONCLUSIONS: It is safe to remove the metal stent of the tracheal tube under the guidance of fluoroscopy, with low complications, and can avoid the long-term placement of the airway stent.

Inferior vena cava filter misplacement in the right ovarian vein and successful removal by loop-snare technique in a patient with inferior vena cava agenesis.

Misplacement of an inferior vena cava (IVC) filter in a gonadal vein is a rare complication of IVC filter placement. We report a case of a filter misplaced in the ovarian vein of a pregnant woman with agenesis of the infrarenal IVC and bilateral lower extremity deep venous thrombosis. The filter was removed by a loop-snare technique through an internal jugular vein. IVC agenesis and dilated right gonadal vein should be kept in mind when an IVC filter is being inserted in the infrarenal location through the jugular approach.

Association between three genetic variants in kallikrein 3 and prostate cancer risk.

BACKGROUND: Epidemiological studies have assessed the association between kallikrein 3 (KLK3) polymorphisms and prostate cancer (PCa) susceptibility. However, published data on this association are somewhat inconclusive. METHODS: Articles investigating the association between three KLK3 (rs1058205, rs2735839, and rs266882) variants and PCa susceptibility were searched from online databases, which included 35,838 patients and 36,369 control participants. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to demonstrate the strength of the association. We also utilized ELISA to detect serum expression of KLK3. In addition, in silico tools were adopted to evaluate the relationship of KLK3 expression and PCa survival time. RESULTS: The overall results indicated that polymorphism T>C of rs1058205 was associated with decreased risk of PCa (allele contrast: OR = 0.75, 95% CI = 0.64-0.88, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.42-0.81, Pheterogeneity < 0.001), particularly in Caucasian population (allele contrast: OR = 0.77, 95% CI = 0.65-0.91, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.41-0.82, Pheterogeneity < 0.001). No association was observed between the polymorphism A>G of rs2735839 and risk of PCa. In addition, no association was observed between polymorphism A>G of rs266882 and risk of PCa. Serum KLK3 levels in PCa patients carrying CC/CT genotypes were statistically lower than those carrying TT genotypes. Conclusion: This meta-analysis suggests that rs1058205 polymorphism of KLK3 is a risk factor for PCa development, polymorphism T>C of rs1058205 is associated with decreased susceptibility to PCa particularly in Caucasian population.

Quercetin nanoparticles display antitumor activity via proliferation inhibition and apoptosis induction in liver cancer cells.

Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables. Quercetin prevents tumor proliferation by inducing cell cycle arrest and is a well known cancer therapeutic agent and autophagy mediator. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles was examined. In this study, we explored the role and possible underlying mechanisms of quercetin nanoparticle in regulation of antitumor activity in liver cancer cells. Treatment with quercetin nanoparticle effectively inhibited the liver cancer cell proliferation, cell migration and colony formation, thus suppressing liver cancer progression. Quercetin nanoparticle also upregulated apoptosis markedly. Further study suggested that quercetin nanoparticle accelerated the cleavage of caspase-9, caspase-3, and induced the up-releasing of cytochrome c (Cyto-c), contributing to apoptosis in liver cancer cells. Quercetin nanoparticles also promoted telomerase reverse transcriptase (hTERT) inhibition through reducing AP-2ß expression and decreasing its binding to hTERT promoter. In addition, quercetin nanoparticle had an inhibitory role in cyclooxygenase 2 (COX-2) via suppressing the NF-κB nuclear translocation and its binding to COX-2 promoter. Quercetin nanoparticle also inactivated Akt and ERK1/2 signaling pathway. Taken together, our results suggested that quercetin nanoparticle had an antitumor effect by inactivating caspase/Cyto-c pathway, suppressing AP-2ß/hTERT, inhibiting NF-κB/COX-2 and impeding Akt/ERK1/2 signaling pathways. Our results provided new mechanistic basis for further investigation of quercetin nanoparticles to find potential therapeutic strategies and possible targets for liver cancer inhibition.

Association of a common genetic variant in RNASEL and prostate cancer susceptibility.

The RNASEL gene (2', 5'-oligoisoadenylate synthetase-dependent) encodes a ribonuclease that plays a significant role in the apoptotic and antiviral activities of interferons. Various studies have used polymorphisms in the RNASEL gene to evaluate prostate cancer risk but studies that show an association between RNASEL Arg462Gln (1385G>A, R462Q, rs486907) polymorphism and prostate cancer risk are somewhat inconclusive. To assess the impact of RNASEL Arg462Gln polymorphism on prostate cancer risk, we conducted a meta-analysis of all available studies including 11,522 patients and 10,976 control subjects. The overall results indicated no positive association between the variant and prostate cancer risk. However, in a subgroup analysis by ethnicity, obvious associations were observed in Hispanic Caucasians for allelic contrast (OR = 1.18, 95% CI = 1.00 - 1.39, Pheterogeneity = 0.010), homozygote comparison (OR = 1.50, 95% CI = 1.02 - 2.20, Pheterogeneity = 0.001), and the recessive genetic model (OR = 1.44, 95% CI = 1.01 - 2.05, Pheterogeneity = 0.002) ; and in African descendants for homozygote comparison (OR = 2.59, 95% CI = 1.29 - 5.19, Pheterogeneity = 0.194) and the recessive genetic model (OR = 2.61, 95% CI = 1.30 - 5.23, Pheterogeneity = 0.195). In conclusion, the RNASEL Arg462Gln polymorphism may contribute to the risk of developing prostate cancer in African descendants and Hispanic Caucasians. Further larger and well-designed studies are warranted to evaluate this association in detail.

Application of combined-type Y-shaped covered metallic stents for the treatment of gastrotracheal fistulas and gastrobronchial fistulas.

OBJECTIVE: To determine the safety and feasibility of combined-type integrated Y-shaped self-expanding covered metallic stents to treat gastrotracheal fistulas (GTFs) and gastrobronchial fistulas (GBFs). METHODS: We retrospectively reviewed the data of 10 patients with postoperative GTFs or GBFs. Depending on the size and location of the fistula and the airway diameter, we custom-designed 2 or 3 stents for each patient. The combined-type stents consisted of a large and a small Y-shaped stent. Under fluoroscopic guidance, the small stent was inserted into the distal part of the involved airway. Then, the large stent was placed at the trachea and carina. The large stent partly overlapped the main body of the small stent. RESULTS: All stents were successfully inserted at the first attempt. Esophageal and airway radiography showed no contrast agent leakage, indicating that the fistula was fully sealed. After the procedure, the patients could resume eating without coughing, and their quality of life improved. Each patient was fully followed up. Six patients died at 3.2 to 8 months of tumors (4 patients), hemoptysis (1 patient), or pulmonary infection (1 patient). In 1 patient, the carinal fistula enlarged 4 months after stenting, and another small Y-shaped stent was inserted to seal the fistula. This patient and the remaining 3 patients are still alive. CONCLUSIONS: Deployment of the combined-type Y-shaped integrated self-expanding covered metallic stent proved to be an effective, safe, and minimally invasive procedure for complex GTFs and GBFs. Our patients tolerated the stents well and had good palliation of their symptoms.

Radiology-guided forceps biopsy and airway stenting in severe airway stenosis.

PURPOSE: We aimed to determine the feasibility, safety, and effectiveness of radiology-guided forceps biopsy and airway stenting in patients with severe airway stenosis. MATERIALS AND METHODS: This study involved 28 patients with severe airway stenosis who underwent forceps biopsy between October 2006 and September 2011. Chest multislice computed tomography was used to determine the location and extent of stenosis. Sixteen patients had tracheal stenosis, two patients had stenosis of the tracheal carina, six patients had stenosis of the left main bronchus, and four patients had stenosis of the right main bronchus. Forceps biopsy and stenting of the stenosed area were performed under fluoroscopic guidance in digital subtraction angiography and the biopsy specimens were analyzed histopathologically. We contacted the patients via phone call and utilized a standardized questionnaire to determine their medical condition during a postoperative three-month follow-up. RESULTS: The technical success rate of radiology-guided forceps biopsy was 100%. Biopsy specimens were obtained in all patients. Dyspnea was relieved immediately after stent placement. No serious complications, such as tracheal hemorrhage or perforation, mediastinal emphysema, or asphyxia, occurred. CONCLUSION: Radiology-guided forceps biopsy and airway stenting can be used for the emergency treatment of severe airway stenosis. This method appears to be safe and effective, and it may be an alternative therapeutic option in patients who cannot tolerate fiberoptic bronchoscopy.

Meta-analysis of epidermal growth factor polymorphisms and cancer risk: involving 9,779 cases and 15,932 controls.

The epidermal growth factor (EGF) pathway stimulates proliferation and differentiation of epidermal and epithelial tissues, and plays an important role in tumorigenesis. The association between EGF polymorphisms and cancer risk is controversial; thus, we performed this meta-analysis. Overall, 41 case-control studies with 9,779 cases and 15,932 controls were retrieved. We found that EGF +61A/G polymorphism increased overall cancer risk (G allele vs. A allele: OR=1.181, 95% CI=1.077-1.295, P(heterogeneity) < 0.001; GG vs. AA: OR=1.370, 95% CI=1.143-1.641, P(heterogeneity) < 0.001; GG+GA vs. AA: OR=1.175, 95% CI=1.047-1.318, P(heterogeneity) < 0.001). In the stratified analysis by cancer type, the +61 G allele was a risk factor for colorectal cancer, esophageal carcinoma, gastric cancer, and hepatocellular carcinoma. Individuals who carried +61G allele had higher cancer susceptibility in mixed and European racial subgroups. An increased association was detected in the hospital-based subgroup. No significant association was found among EGF -1380A/G, -1744G/A, rs6983267T/G polymorphisms and cancer risk.

Meta-analysis of MMP2 -1306T allele as a protective factor in digestive cancer.

BACKGROUND AND AIMS: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity on matrix proteins and abolishes a Sp-1 binding site and consequently decreases its activity. Many studies have been carried out on the association between MMP2 -1306C/T polymorphism and digestive cancer risk, but results were somewhat controversial and underpowered. METHODS: To examine the risk of digestive cancer associated with -1306C/T polymorphism of MMP2, we performed a meta-analysis of ten case-control studies. Eligible studies were identified by searching the electronic literature using Pubmed and Embase. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. RESULTS: Overall, we found that -1306T allele can decrease digestive cancer risk in three different genotype models (T-allele vs. C-allele, OR=0.73, 95% CI: 0.54-0.98, p=0.034; TC vs. CC, OR=0.64, 95% CI: 0.53-0.78, p <0.001; TT+TC vs. CC, OR=0.68, 95% CI: 0.53-0.86, p=0.002). Similarly, in the stratified analysis by cancer type, ethnicity and source of control, significantly decreased cancer risk was indicated. Moreover, in the subgroup of smokers, -1306T allele may protect people against digestive cancer risk (TT+TC vs. CC, OR=0.71, 95% CI: 0.51-0.98, p=0.037). CONCLUSIONS: Our meta-analysis showed evidence that MMP2 -1306T allele may be a protective factor for digestive cancer risk as well as a low-penetrance susceptibility digestive cancer biomarker.

1858 C/T polymorphism of the protein tyrosine phosphatase nonreceptor 22 gene and rheumatoid arthritis risk in europeans: a meta-analysis.

BACKGROUND AND AIMS: A single nucleotide polymorphism (SNP) of the protein tyrosine phosphatase nonreceptor gene (PTPN22) confers susceptibility to rheumatoid arthritis (RA) and certain other classical autoimmune diseases. The association between PTPN22 1858C/T polymorphism and the risk of RA is still controversial and ambiguous; therefore, we performed this meta-analysis to confirm some relationships. METHODS: We conducted a search in the PubMed database without a language limitation, covering all papers published until June 20, 2011. Overall, 19 case-control studies with 11,727 cases and 12,640 controls were retrieved based on the search criteria for RA susceptibility related to the 1858C/T polymorphism. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of this association. Publication bias was assessed with Eggers test. RESULTS: We found that PTPN22 1858C/T polymorphism could increase RA risk in overall genetic models in Europeans (T-allele vs. C-allele, OR = 1.54, 95% CI = 1.47-1.62, P(heterogeneity) = 0.143; TT vs. CC, OR = 2.86, 95% CI = 2.29-3.57, P(heterogeneity) = 0.302; TC vs. CC, OR = 1.45, 95% CI = 1.38-1.53, P(heterogeneity) = 0.273; TT + TC vs. CC, OR = 1.49, 95% CI = 1.42-1.56, P(heterogeneity) = 0.208; TT vs. TC + CC, OR = 2.52, 95% CI = 1.95-3.25, P(heterogeneity) = 0.296). Furthermore, significant relationships were detected among PTPN22 1858C/T polymorphism and RF(+) or RF(-) RA risk. No obvious evidence of publication bias was detected in the overall analysis. CONCLUSIONS: Our study indicated that PTPN22 1858T allele was significantly associated with increased RA risk.

Development of a sensitive Indirect Competitive Enzyme-Linked Immunosorbent Assay (ic-ELISA) based on the monoclonal antibody for the detection of the imidaclothiz residue.

An indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) based on monoclonal antibodies (MoAbs) for imidaclothiz was developed. The hapten of imidaclothiz was synthesized and conjugated to bovine serum albumin (BSA) and ovalbumin (OVA) to form the artificial antigens. MoAbs were obtained by immunizing BALB/c mice. Under the optimized conditions (10% methanol, 0.14 M Na(+), and pH 7.4), the half-maximal inhibition concentration (IC(50)) was 0.0875 ± 0.0034 mg/L and the limit of detection (IC(20)) was 0.0178 ± 0.0018 mg/L for imidaclothiz. There were no obvious cross-reactivities with most of the structural analogues of neonicotinoid insecticides, except imidacloprid. The recoveries of imidaclothiz in environmental and agricultural samples, including tap water, paddy water, soil, and cabbage, ranged from 80.43 to 113.83%, well within the requirements of residue detection. These results showed that this immunoassay could be used for the determination of imidaclothiz in environmental and agricultural samples.