Lymph node pick up by separate stations: Option or necessity

AIM: To evaluate whether lymph node pick up by separate stations could be an indicator of patients submitted to appropriate surgical treatment. METHODS: One thousand two hundred and three consecutive gastric cancer patients submitted to radical resection in 7 general hospitals and for whom no information was available on the extension of lymphatic dissection were included in this retrospective study. RESULTS: Patients were divided into 2 groups: group A, where the stomach specimen was directly formalinfixed and sent to the pathologist, and group B, where lymph nodes were picked up after surgery and fixed for separate stations. Sixty-two point three percent of group A patients showed 16 retrieved lymph nodes compared to 19.4% of group B(P 0.0001). Group B(separate stations) patients had significantly higher survival rates than those in group A [46.1 mo(95%CI: 36.5-56.0) vs 27.7 mo(95%CI: 21.3-31.9); P = 0.0001], independently of T or N stage. In multivariate analysis, group A also showed a higher risk of death than group B(HR = 1.24; 95%CI: 1.05-1.46).CONCLUSION: Separate lymphatic station dissection increases the number of retrieved nodes, leads to better tumor staging, and permits verification of the surgical dissection. The number of dissected stations could potentially be used as an index to evaluate the quality of treatment received.     

Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration

Parkin and the glial cell line–derived neurotrophic factor (GDNF) receptor RET have both been independently linked to the dopaminergic neuron degeneration that underlies Parkinson’s disease (PD). In the present study, we demonstrate that there is genetic crosstalk between parkin and the receptor tyrosine kinase RET in two different mouse models of PD. Mice lacking both parkin and RET exhibited accelerated dopaminergic cell and axonal loss compared with parkin-deficient animals, which showed none, and RET-deficient mice, in which we found moderate degeneration. Transgenic expression of parkin protected the dopaminergic systems of aged RET-deficient mice. Downregulation of either parkin or RET in neuronal cells impaired mitochondrial function and morphology. Parkin expression restored mitochondrial function in GDNF/RET-deficient cells, while GDNF stimulation rescued mitochondrial defects in parkin-deficient cells. In both cases, improved mitochondrial function was the result of activation of the prosurvival NF-κB pathway, which was mediated by RET through the phosphoinositide-3-kinase (PI3K) pathway. Taken together, these observations indicate that parkin and the RET signaling cascade converge to control mitochondrial integrity and thereby properly maintain substantia nigra pars compacta dopaminergic neurons and their innervation in the striatum. The demonstration of crosstalk between parkin and RET highlights the interplay in the protein network that is altered in PD and suggests potential therapeutic targets and strategies to treat PD.     

Mechanisms of Fibrosis in Steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a frequent cause of cirrhosis and may lead to liver-related mortality. In Western countries, NASH is the most common liver disease and may progress to advanced fibrosis or cirrhosis in a significant portion of cases. Moreover, NASH, even in the absence of cirrhosis, is associated with the development of hepatocellular carcinoma. An increased risk of cardiovascular events and/or diabetes represents another major problem in these patients. In this review, we discuss recent data on the basic mechanisms leading to the development of fibrosis in nonalcoholic steatohepatitis, in particular those which may identify novel approaches to treatment.