Pediatric robotic surgery: early assessment.

OBJECTIVES: This article reviews the evidence regarding the feasibility, safety, benefits, limitations, and costs of robotically assisted surgery in children, evaluates how the technology compares with other pediatric surgical techniques, and provides insights about the near and more-distant future of the technology. METHODS: The peer-reviewed medical pediatric literature was searched for studies that provided evidence of the feasibility and safety of robotic surgery in children and for studies that compared pediatric robotic surgery with conventional laparoscopic surgery or open surgery. RESULTS: A total of 8 case series and 5 studies comparing robotic surgery with open or conventional laparoscopic surgery met the selection criteria for review. A few small studies that focused on rare complex surgical procedures also were reviewed. All studies were designed to evaluate the feasibility and safety of robotic surgery in children. None of the studies was randomized, and some studies had a retrospective design. These studies demonstrated that a number of routine, robotically assisted, laparoscopic and thoracic procedures were feasible and safe when performed by surgeons experienced in the technique, although robotic surgery did not provide superior outcomes, compared with traditional laparoscopic and open surgery. The advantages of the robotic system were best seen in complex procedures that involved areas that were difficult to access and in procedures in which dissection of delicate, anatomic structures was required. CONCLUSIONS: Robotic surgery is feasible and safe for a number of pediatric surgical procedures, but evidence that it offers better clinical outcomes than conventional open or laparoscopic techniques is lacking.

A functional NF-kappaB enhancer element in the first intron contributes to the control of c-fos transcription.

Eukaryotic gene transcription is controlled not only by gene promoters but also by intragenic cis-elements. Such regulation is important for the transcription of immediate early genes (IEGs) and in particular for the c-fos gene, the first intron of which contains many potential transcription factor binding elements. In the present study, we addressed the intronic control of c-fos transcription by the NF-kappaB signalling pathway in the neuroendocrine cell line GH4C1. Tumour necrosis factor alpha (TNFalpha) activating the NF-kappaB signalling pathway induced transcription of the c-fos gene and enhanced thyrotropin-releasing hormone-stimulated (TRH-stimulated) c-fos transcription. To examine the effects of NF-kappaB, the presumed NF-kappaB binding sequence in the first intron was mutated or deleted from c-fos reporter gene constructs. When GH4C1 cells transfected with the reporter constructs were stimulated by TNFalpha, the induced expression was significantly diminished. Double-stranded short DNA with the intronic NF-kappaB binding consensus sequence interacted directly with NF-kappaB p50 protein in vitro; mutation of 3 nucleotides destroying the consensus abolished the in vitro interaction. The importance of NF-kappaB for c-fos expression was also supported by RNA interference experiments; knock-down of NF-kappaB p50 suppressed TNFalpha-induced c-fos expression. In addition, chromatin immunoprecipitation indicated that NF-kappaB occupied the first intron of the c-fos gene in vivo. In conclusion, NF-kappaB enhances c-fos transcription via the direct binding to a response element situated in the first intron.

Spontaneous calcium oscillations control c-fos transcription via the serum response element in neuroendocrine cells.

In excitable cells the localization of Ca2+ signals plays a central role in the cellular response, especially in the control of gene transcription. To study the effect of localized Ca2+ signals on the transcriptional activation of the c-fos oncogene, we stably expressed various c-fos beta-lactamase reporter constructs in pituitary AtT20 cells. A significant, but heterogenous expression of c-fos beta-lactamase was observed in unstimulated cells, and a further increase was observed using KCl depolarization, epidermal growth factor (EGF), pituitary adenylate cyclase-activating polypeptide (PACAP), and serum. The KCl response was almost abolished by a nuclear Ca2+ clamp, indicating that a rise in nuclear Ca2+ is required. In contrast, the basal expression was not affected by the nuclear Ca2+ clamp, but it was strongly reduced by nifedipine, a specific antagonist of l-type Ca2+ channels. Spontaneous Ca2+ oscillations, blocked by nifedipine, were observed in the cytosol but did not propagate to the nucleus, suggesting that a rise in cytosolic Ca2+ is sufficient for basal c-fos expression. Inactivation of the c-fos promoter cAMP/Ca2+ response element (CRE) had no effect on basal or stimulated expression, whereas inactivation of the serum response element (SRE) had the same marked inhibitory effect as nifedipine. These experiments suggest that in AtT20 cells spontaneous Ca2+ oscillations maintain a basal c-fos transcription through the serum response element. Further induction of c-fos expression by depolarization requires a nuclear Ca2+ increase.