ABSTRACT
BACKGROUND: Two strategies for same-admission cholecystectomy in mild gallstone pancreatitis (MGP) exist: early surgery (within 48-72 h from admission) and delayed surgery until resolution of symptoms and normalization of pancreatic tests. METHODS: This was a single-center, open-label RCT. Patients with MGP according to revised Atlanta classification-2012 and SIRS criteria were randomly assigned to early laparoscopic cholecystectomy (E-LC) within 72 h from admission or delayed laparoscopic cholecystectomy (D-LC). Laparoscopic-endoscopic rendezvous was performed when common bile duct stones were found at systematic intraoperative cholangiography. The primary outcome was length of stay (LOS), and the secondary outcomes were complications at 90 days, need for ERCP/choledocolithiasis, conversion, and re-admission. One year of follow-up was carried-on. RESULTS: At interim analysis, 52 patients were randomized (26 E-LC, 26 D-LC). E-LC versus D-LC was associated with a significantly shorter LOS (median 58 versus 167 h; P = 0.001). There were no differences in ERCP necessity for choledocolithiasis between the two approaches (E-LC 26.9% versus D-LC 23.1%, P = 1.00). No differences in postoperative complications were found. CONCLUSIONS: E-LC approach in patients with MGP significantly reduced LOS and was not associated with clinically relevant postoperative complications. TRIAL REGISTRATION: clinicaltrials.gov (NCT02590978).
Subject(s)
Cholecystectomy, Laparoscopic , Gallstones/surgery , Length of Stay , Pancreatitis/surgery , Postoperative Complications/epidemiology , Time-to-Treatment , Adult , Aged , Cholangiopancreatography, Endoscopic Retrograde , Choledocholithiasis/diagnosis , Choledocholithiasis/epidemiology , Female , Gallstones/complications , Gallstones/diagnosis , Humans , Male , Middle Aged , Pancreatitis/complications , Pancreatitis/diagnosis , Patient Readmission , Postoperative Complications/diagnosis , Severity of Illness Index , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: ALPPS procedure has been introduced to increase the volume of future liver remnant. The mechanisms underlying the accelerated regeneration observed with ALPPS are unknown. It was hypothesized that AMPK/mTOR is activated as an integrating pathway for metabolic signals leading to proliferation and cell growth. Our aim was to analyze increase in liver volume, proliferation parameters and expression of AMPK/mTOR pathway-related molecules in patients undergoing ALPPS. METHODS: A single center prospective study of patients undergoing ALPPS was performed from 2013 to 2015. Liver and serum samples, clinical laboratory results and CT-scan data were obtained. ELISA, Ki-67 immunostaining and qRT-PCR were performed in deportalized and remnant liver tissue in both stages of the procedure. RESULTS: 11 patients were enrolled. Remnant liver volume increased 112 ± 63% (p < 0.05) in 9.1 ± 1.6 days. Proliferation-related cytokines IL-6, TNF-α, HGF and EGF significantly increased, while higher Ki-67 immunostaining and cyclin D expression were observed in remnant livers after ALPPS. mTOR, S6K1, 4E-BP1, TSC1 and TSC2 expression were significantly increased in remnant livers at second stage, while AMPK and Akt increased only in deportalized liver samples. CONCLUSION: Rapid liver regeneration with ALPPS might be associated with hepatocyte proliferation induced by mTOR pathway activation.
Subject(s)
Hepatectomy/methods , Liver Regeneration , Liver/blood supply , Liver/surgery , Portal Vein/surgery , TOR Serine-Threonine Kinases/metabolism , AMP-Activated Protein Kinases/metabolism , Aged , Cell Cycle Proteins/metabolism , Cell Proliferation , Cytokines/metabolism , Enzyme Activation , Female , Hepatectomy/adverse effects , Hepatocytes/enzymology , Hepatocytes/pathology , Humans , Ligation , Liver/diagnostic imaging , Liver/enzymology , Liver Circulation , Male , Middle Aged , Portal Vein/physiopathology , Prospective Studies , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Time Factors , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
UNLABELLED: Recently, we reported that oxidative stress due to 3,3',5-triiodothyronine (T(3))-induced calorigenesis up-regulates the hepatic expression of mediators promoting cell protection. In this study, T(3) administration in rats (single dose of 0.1 mg/kg intraperitoneally) induced significant depletion of reduced liver glutathione (GSH), with higher protein oxidation, O(2) consumption, and Kupffer cell function (carbon phagocytosis and carbon-induced O(2) uptake). These changes occurred within a period of 36 hours of T(3) treatment in animals showing normal liver histology and lack of alteration in serum AST and ALT levels. Partial hepatic ischemia-reperfusion (IR) (1 h of ischemia via vascular clamping and 20 h reperfusion) led to 11-fold and 42-fold increases in serum AST and ALT levels, respectively, and significant changes in liver histology, with a 36% decrease in liver GSH content and a 133% increase in that of protein carbonyls. T(3) administration in a time window of 48 hours was substantially protective against hepatic IR injury, with a net 60% and 90% reduction in liver GSH depletion and protein oxidation induced by IR, respectively. Liver IR led to decreased DNA binding of nuclear factor-kappaB (NF-kappaB) (54%) and signal transducer and activator of transcription 3 (STAT3) (53%) (electromobility shift assay), with 50% diminution in the protein expression of haptoglobin (Western blot), changes that were normalized by T(3) preconditioning. CONCLUSION: T(3) administration involving transient oxidative stress in the liver exerts significant protection against IR injury, a novel preconditioning maneuver that is associated with NF-kappaB and STAT3 activation and acute-phase response.
