Extended Lymphadenectomy in Patients With Pancreatic Cancer Is Debatable

Lymph node staging is one of the most important factors in determining the prognosis after resection of pancreatic ductal adenocarcinoma. Despite ongoing efforts to further refine lymph node staging, the debate on the extent of lymphadenectomy during pancreaticoduodenectomy is still open. The purpose of this review was to summarize the evidence about performing standard lymphadenectomy during curative resection of pancreatic cancer. All four prospective randomized controlled trials published concluded that extended lymphadenectomy does not contribute to better oncologic outcome for patients with adenocarcinoma of the pancreatic head. Indeed, one major drawback of extended lymphadenectomy is the higher risk of persistent postoperative diarrhea. No prospective randomized studies could be found on the role of extended lymphadenectomy in patients with adenocarcinoma of the corpus and tail. Based on current evidence there is no indication that extended lymphadenectomy should be performed routinely during resection of pancreatic cance

NMDA receptor dysfunction contributes to impaired brain-derived neurotrophic factor-induced facilitation of hippocampal synaptic transmission in a Tau transgenic model.

While the spatiotemporal development of Tau pathology has been correlated with occurrence of cognitive deficits in Alzheimer's patients, mechanisms underlying these deficits remain unclear. Both brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB play a critical role in hippocampus-dependent synaptic plasticity and memory. When applied on hippocampal slices, BDNF is able to enhance AMPA receptor-dependent hippocampal basal synaptic transmission through a mechanism involving TrkB and N-methyl-d-Aspartate receptors (NMDAR). Using THY-Tau22 transgenic mice, we demonstrated that hippocampal Tau pathology is associated with loss of synaptic enhancement normally induced by exogenous BDNF. This defective response was concomitant to significant memory impairments. We show here that loss of BDNF response was due to impaired NMDAR function. Indeed, we observed a significant reduction of NMDA-induced field excitatory postsynaptic potential depression in the hippocampus of Tau mice together with a reduced phosphorylation of NR2B at the Y1472, known to be critical for NMDAR function. Interestingly, we found that both NR2B and Src, one of the NR2B main kinases, interact with Tau and are mislocalized to the insoluble protein fraction rich in pathological Tau species. Defective response to BDNF was thus likely related to abnormal interaction of Src and NR2B with Tau in THY-Tau22 animals. These are the first data demonstrating a relationship between Tau pathology and synaptic effects of BDNF and supporting a contribution of defective BDNF response and impaired NMDAR function to the cognitive deficits associated with Tauopathies

ALPPS Offers a Better Chance of Complete Resection in Patients with Primarily Unresectable Liver Tumors Compared with Conventional-Staged Hepatectomies: Results of a Multicenter Analysis

Background: Portal vein occlusion to increase the size of the future liver remnant (FLR) is well established, using portal vein ligation (PVL) or embolization (PVE) followed by resection 4-8weeks later. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) combines PVL and complete parenchymal transection, followed by hepatectomy within 1-2weeks. ALPPS has been recently introduced but remains controversial. We compare the ability of ALPPS versus PVE or PVL for complete tumor resection. Methods: A retrospective review of all patients undergoing ALPPS or conventional staged hepatectomies using PVL or PVE at four high-volume HPB centres between 2003 and 2012 was performed. Patients with primary liver tumors and liver metastases were included. Primary endpoint was complete tumor resection. Secondary endpoints include 90-day mortality, complications, FLR increase, time to resection, and tumor recurrence. Results: Forty-eight patients with ALPPS were compared with 83 patients with conventional-staged hepatectomies. Eighty-three percent (40/48 patients) of ALPPS patients achieved complete resection compared with 66% (55/83 patients) in PVE/PVL (odds ratio 3.34, p=0.027). Ninety-day mortality in ALPPS and PVE/PVL was 15 and 6%, respectively (p=0.2). Extrapolated growth rate was 11 times higher in ALPPS (34.8cc/day; interquartile range (IQR) 26-49) compared with PVE/PVL (3cc/day; IQR2-6; p=0.001). Tumor recurrence at 1year was 54 versus 52% for ALPPS and PVE/PVL, respectively (p=0.7). Conclusions: This study provides evidence that ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors at the cost of a high mortality. The technique is promising but should currently not be used outside of studies and registries

ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors compared with conventional-staged hepatectomies: results of a multicenter analysis

BACKGROUND: Portal vein occlusion to increase the size of the future liver remnant (FLR) is well established, using portal vein ligation (PVL) or embolization (PVE) followed by resection 4-8 weeks later. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) combines PVL and complete parenchymal transection, followed by hepatectomy within 1-2 weeks. ALPPS has been recently introduced but remains controversial. We compare the ability of ALPPS versus PVE or PVL for complete tumor resection. METHODS: A retrospective review of all patients undergoing ALPPS or conventional staged hepatectomies using PVL or PVE at four high-volume HPB centres between 2003 and 2012 was performed. Patients with primary liver tumors and liver metastases were included. Primary endpoint was complete tumor resection. Secondary endpoints include 90-day mortality, complications, FLR increase, time to resection, and tumor recurrence. RESULTS: Forty-eight patients with ALPPS were compared with 83 patients with conventional-staged hepatectomies. Eighty-three percent (40/48 patients) of ALPPS patients achieved complete resection compared with 66 % (55/83 patients) in PVE/PVL (odds ratio 3.34, p = 0.027). Ninety-day mortality in ALPPS and PVE/PVL was 15 and 6 %, respectively (p = 0.2). Extrapolated growth rate was 11 times higher in ALPPS (34.8 cc/day; interquartile range (IQR) 26-49) compared with PVE/PVL (3 cc/day; IQR2-6; p = 0.001). Tumor recurrence at 1 year was 54 versus 52 % for ALPPS and PVE/PVL, respectively (p = 0.7). CONCLUSIONS: This study provides evidence that ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors at the cost of a high mortality. The technique is promising but should currently not be used outside of studies and registries

ETUDE DE DEUX PROTEINES VIRALES, REV DE HIV-1 ET EB2 DE EBV, ASSURANT L'EXPORT NUCLEAIRE D'ARN MESSAGERS NON EPISSES

LYON-ENS Sciences (693872304) / SudocSudocFranceF

STRUCTURE DU COMPOSANT AVAL DE L'ORIGINE DE REPLICATION ORILYT DU VIRUS D'EPSTEIN-BARR ET CARACTERISATION DE LA PROTEINE K8 DU VIRUS HHV8 (DOCTORAT DIFFERENCIATION, GENETIQUE ET IMMUNOLOGIE)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF