Study Type – Therapy (systematic review) Level of Evidence 1a What's known on the subject? and What does the study add? There are several surgical techniques for the treatment of varicocele in infertile men, including open non‐microsurgical, laparoscopic and microsurgical varicocelectomy. It is currently unclear, however, which is the most beneficial method for patients. The present meta‐analysis found that microsurgical varicocelectomy is the most effective and least morbid method among the three varicocelectomy techniques for treating varicocele in infertile men. OBJECTIVE To compare various techniques of open non‐microsurgical, laparoscopic or microsurgical varicocelectomy procedures to describe the best method for treating varicocele in infertile men. PATIENTS AND METHODS We searched PubMed, Embase, the Cochrane Library, the Institute for Scientific Information (ISI) – Science Citation Index and the Chinese Biomedicine Literature Database up to June 2011. Only randomized controlled trials (RCTs) were included in the present study. The outcome measures assessed were pregnancy rate (primary), the incidence of recurrent varicocele, time to return to work, the incidence of postoperative hydrocele and operation duration (secondary). Two authors independently assessed the study quality and extracted data. All data were analysed using Review Manager (version 5.0). RESULTS The present study included four randomized controlled trials comprising 1,015 patients in total. At the follow‐up endpoints, patients who had undergone microsurgery showed a significant advantage over those who had undergone open varicocelectomy in terms of pregnancy rate (odds ratio [OR]= 1.63, 95% confidence interval [CI]: 1.19–2.23]. There was no significant difference between laparoscopic and open varicocelectomy (OR = 1.11, 95% CI: 0.65–1.88) or between microsurgery and laparoscopic varicocelectomy (OR = 1.37, 95% CI: 0.84–2.24). The incidences of recurrent varicocele and postoperative hydrocele were significantly lower after microsurgery than after laparoscopic or open varicocelectomy. The time to return to work after microsurgery and laparoscopic varicocelectomy was significantly shorter than that after open varicocelectomy. The operation duration of microsurgical varicocelectomy was longer than that of laparoscopic or open varicocelectomy. CONCLUSIONS Current evidence indicates that microsurgical varicocelectomy is the most effective and least morbid method among the three varicocelectomy techniques for treating varicocele in infertile men. More high‐quality, multicentre, long‐term RCTs are required to verify the findings.

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Background/Aims: To evaluate the efficacy of tamsulosin as a medical expulsive therapy of ureteral stones. Methods: We searched PubMed, EMBASE, the Cochrane Library, and ISI-Science Citation Index up to December 2011. All randomized controlled trials were identified in which patients were randomized to receive either tamsulosin or standard therapy with/without placebo for ureteral stones. Outcome measures assessed were overall stone expulsion rate (primary) and expulsion time, and the number of pain episodes (secondary). Three authors independently assessed study quality and extracted data. All data were analyzed using RevMan 5.0. Results: Twenty-nine trials with a total of 2,763 patients met the inclusion criteria. The pooled analysis showed a 19% improvement in stone clearance with tamsulosin. According to the doses of tamsulosin, the pooling effects of tamsulosin were analyzed, with a higher expulsion rate obtained than in controls. Compared with calcium channel blockers, there was a higher stone expulsion rate in tamsulosin. In addition, a shorter expulsion time, fewer colic episodes and adverse effects were observed. Conclusions: Tamsulosin is a safe and effective medical expulsive therapy choice for ureteral stones. It should be recommended for most patients with distal ureteral stones before stones are 10 mm in size. In future, high-quality multicenter, randomized and placebo-controlled trials are needed to evaluate the outcome.

Background Circular RNA (circRNA) is emerging as an important player in human diseases, especially cancer. In our previous study, we identified a series of deregulated circRNAs in hepatocellular carcinoma (HCC) by performing circRNA microarray expression profile. Here, we aimed to explore the role of circ-LRIG3 (hsa_circ_0027345) in HCC. Methods qRT-PCR and western blot were used to asses gene and protein expression, respectively. CCK-8, EdU and Transwell assays were used to detect cell proliferation, migration and invasion. GSEA software was applied to analyze the pathway related to circ-LRIG3. Co-IP, RIP and ChIP assays were used to identify the positive feedback axis of circ-LRIG3/EZH2/STAT3. Animal study was carried to test the role of circ-LRIG3 in vivo. Results Circ-LRIG3 was notably upregulated in HCC and promoted HCC cell proliferation, migration, invasion and reduced apoptosis. Circ-LRIG3 formed a ternary complex with EZH2 and STAT3, facilitating EZH2-induced STAT3 methylation and subsequent phosphorylation, resulting in the activation of STAT3 signaling. In turn, activated STAT3 could directly bind to circ-LRIG3 promoter to increase circ-LRIG3 transcription activity, thus forming a positive feedback loop. The animal models showed that exogenous expression of circ-LRIG3 enhanced tumorigenicity and metastasis in vivo, whereas these effects were blocked after treatment with C188–9, a specific STAT3 small-molecule inhibitor. Clinically, high circ-LRIG3 was closely linked with aggressive clinicopathological features and was identified as an independent risk prognostic factor of overall survival. Importantly, plasma circ-LRIG3 was found to be a highly sensitive and specific non-invasive diagnostic indicator for HCC. Conclusions Our study reveals the carcinogenic role of circ-LRIG3 in HCC, which may provide a new therapeutic target for HCC patients.

Background: AnassociationbetweenN-acetyltransferase2(NAT2)slowacetylationandbladdercancerhasbeen consistently observed in epidemiologic studies. However, evidence has been mainly derived from case-control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case-controlstudy nested in the European Prospective Investigation into Cancer and Nutrition.Methods: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative jobexposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood samples.Results: Occupational exposure to aromatic amines and PAH was associated with an increased bladder cancer risk [upper tertile of the distribution of the exposure score: OR ¼ 1.37; 95% confidence interval (CI), 1.02-1.84, and OR ¼ 1.50; 95% CI, 1.09-2.05, respectively]. NAT2 slow acetylation did not modify these risk estimates and was not itself associated with bladder cancer risk (OR ¼ 1.02; 95% CI, 0.81-1.29).Conclusions: These findings confirm established or suspected occupational risk factors but not the anticipated role of NAT2 slow acetylation in bladder cancer. No interaction was detected between NAT2 and any exposure of interest, including smoking.Impact: Genetic testing for NAT2 would be inappropriate in occupational settings. Cancer Epidemiol Biomarkers Prev; 22(11); 2055-65. Ó2013 AACR.

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This meta-analysis suggested that prophylactic μ-opioid agonists fentanyl, remifentanil, sufentanil, and alfentanil could significantly decrease the incidence of EA under sevoflurane anesthesia in children compared to placebo. Considering the limitations of the included studies, more clinical studies are required.