The evolutionarily conserved Six1-Eya1 transcription complex is central to mammalian organogenesis, and deletion of these genes in mice results in developmental anomalies of multiple organs that recapitulate human branchio-oto-renal (BOR) and DiGeorge syndromes. Here, we report that both Six1 and Eya1 are strongly expressed in the peri-cloacal mesenchyme (PCM) surrounding the cloaca, the terminal end of hindgut dilation. Six1 and Eya1 are absent from the intra-cloacal mesenchyme (ICM), a cell mass that divides the cloaca into dorsal hindgut and ventral urogenital sinus. Deletion of either or both Six1 and Eya1 genes results in a spectrum of genitourinary tract defects including persistent cloaca - hypoplastic perineum tissue between external urogenital and anorectal tracts; hypospadias - ectopic ventral positioning of the urethral orifice; and hypoplastic genitalia. Analyses of critical signaling molecules indicate normal expression of Shh in the cloaca and cloaca-derived endodermal epithelia. Using a Cre/loxP genetic fate mapping strategy, we demonstrate that Six1-positive PCM progenitors give rise to the most caudal structures of the body plan including the urogenital and anorectal complex, and the perineum region. Thus, Six1 and Eya1 are key regulators of both upper and lower urinary tract morphogenesis. Results from this study uncover essential roles of the PCM progenitors during genitourinary tract formation.

BackgroundInterleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. Few studies have investigated polymorphisms and serum/plasma levels of IL-27 in diseases including cancers. This study has analyzed the associations of IL-27 gene polymorphisms, as well as plasma levels of IL-27, with susceptibility to bladder cancer and clinical outcome.MethodsThree hundred and thirty-two patients (nonmuscle-invasive bladder cancer (NMIBC)/muscle-invasive bladder cancer (MIBC): 176/156) included in a 60-month follow-up program and 499 controls were enrolled. Two single nucleotide polymorphisms (SNPs), rs153109 and rs17855750, were genotyped by polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP) method. Plasma concentration of IL-27 was determined by ELISA in 124 patients (NMIBC/MIBC: 50/74) and 151 controls.ResultsSignificantly increased risk for bladder cancer was associated with AG/GG genotypes of rs153109 (P = 0.029). No GG genotype of rs17855750 was observed in controls, while 4 patients were found to be GG homozygotes, suggesting GG genotype may be associated with bladder cancer risk (P = 0.006). For bladder cancer patients, SNP rs17855750 was also associated with increased risk for MIBC. For MIBC patients, but not NMIBC, TG/GG genotypes of rs17855750 turned out to be a protective factor for overall survival (P = 0.035). Significantly reduced plasma levels of IL-27 were observed in both NMIBC and MIBC patients compared with controls (P < 0.0001).ConclusionOur data suggest that polymorphisms and reduced plasma levels of IL-27 may predict the susceptibility to bladder cancer, and rs17855750 may be a useful marker to distinguish patients with high risk of death.

Objectives: To provide a systematic review and meta-analysis of studies comparing ureterolithotripsy (URS) with percutaneous nephrolithotripsy (PCNL) or laparoscopic ureterolithotomy (LU) techniques for the management of large proximal ureteral stones (diameter greater than 10 mm). Methods: A literature search was performed using PubMed, EMBASE, EBSCO, Web of Science, and Cochrane Library to identify suitable studies until November 2016. We used weighted mean difference to measure operative time and hospital stay, OR to measure stone free rate (SFR), and complication rate. Subgroup analyses were assessed for heterogeneity. Results: Fourteen publications strictly met our eligibility criteria of which 7 were randomized control studies (RCTs) and 7 non-RCTs. Meta-analysis of extractable data showed that LU and PCNL had higher SFR than URS. URS led to a similar hospital stay like that of LU. However, it had a shorter operative time and lower complication rate than LU. When we compared URS with PCNL, we found a shorter hospital stay in the URS group. However, there was no significant difference in terms of the operative time and complication rate between URS and PCNL. Conclusion: URS should be considered standard therapy for treating large proximal ureteral stones.