“Technological” approach versus clamp crushing technique for hepatic parenchymal transection: A comparative study

We evaluated the feasibility and effectiveness of combining two different electronic devices, the ultrasonic dissector (UD) and the harmonic scalpel (HS), during hepatic resection. One hundred consecutive patients underwent liver resection using UD plus HS between January and December 2004 (UD + HS group). The ultrasonic dissector was used to fracture liver parenchyma and the uncovered vessel was sealed using the HS. Surgical outcomes were compared with 100 consecutive patients who underwent liver resection using the clamp crushing method. Operative variables, postoperative liver function, hospital stay, and type and number of complications were compared. The two groups were equivalent in term of demographic and pathologic variables. The UD + HS group had a decreased blood loss (500 ml versus 700 ml, P=0.005), number of patients transfused (22 versus 39, P=0.009), tumor exposure at the transection surface (4 versus 12, P=00.012), and hospital stay (7 versus 8.5 days, P=0.020). Postoperative major complications, in particular, fluid collection and biliary fistula, were significantly less frequent in the UD+HS group (2 versus 9, P=0.030). A longer operative time was recorded in the UD+HS group (385 versus 330 minutes, P=0.001). The combined use of UD with HS allows liver resection to be safely performed, with the advantage of reducing blood losses and surgery-related complications. The only major disadvantage may be a longer transection time.     

Serum uric acid and multiple sclerosis

Several studies indicate that patients with multiple sclerosis (MS) have low serum levels of the endogenous antioxidant uric acid (UA), although it has not been established whether UA is primarily deficient or secondarily reduced due to its peroxynitrite scavenging activity. We measured serum urate levels in 124 MS patients and 124 age- and sex-matched controls with other neurological diseases. In addition, we compared UA levels when MS patients were stratified according to disease activity (by means of clinical examination and MRI), duration, disability and course. MS patients had significantly lower serum urate levels than controls (p= 0.001). However, UA levels did not significantly correlate with disease activity, duration, disability or course. Our study favors the view that reduced UA in MS is a primary, constitutive loss of protection against oxidative agents, which deserves further pathogenetic elucidation aimed at future therapeutic strategies. Received: 16 January 2002 / Accepted in revised form: 8 July 2002 This work was partially presented at the 4^th EFNS Congress in Lisbon, Portugal, 7–11 September 1999 and has been published in abstract form in the European Journal of Neurology (Eur J Neurol, 1999, pp. 50–51). Correspondence to S. Sotgiu     

JC polyomavirus expression and bell-shaped regulation of its SF2/ASF suppressor during the follow-up of multiple sclerosis patients treated with natalizumab

Natalizumab is effective against multiple sclerosis (MS), but is associated with progressive multifocal leukoencephalopathy (PML), fatal disease caused by the JCV polyomavirus. The SF2/ASF (splicing factor2/alternative splicing factor) inhibits JCV in glial cells. We wondered about SF2/ASF modulation in the blood of natalizumab-treated patients and if this could influence JCV reactivation. Therefore, we performed a longitudinal study of MS patients under natalizumab, in comparison to patients under fingolimod and to healthy blood donors. Blood samples were collected at time intervals. The expression of SF2/ASF and the presence and expression of JCV in PBMC were analyzed. A bell-shaped regulation of SF2/ASF was observed in patients treated with natalizumab, increased in the first year of therapy, and reduced in the second one, while slightly changed, if any, in patients under fingolimod. Notably, SF2/ASF was up-regulated, during the first year, only in JCV DNA-positive patients, or with high anti-JCV antibody response; the expression of the JCV T-Ag protein in circulating B cells was inversely related to SF2/ASF protein expression. The SF2/ASF reduction, parallel to JCV activation, during the second year of therapy with natalizumab, but not with fingolimod, may help explain the increased risk of PML after the second year of treatment with natalizumab, but not with fingolimod. We propose that SF2/ASF has a protective role against JCV reactivation in MS patients. This study suggests new markers of disease behavior and, possibly, help in re-evaluations of therapy protocols.     

Impact of age on the outcome of liver resections

The purpose of this study was to evaluate the influence of age on the outcome of liver resections. One hundred five consecutive hepatic resections were divided into two groups: > or = 65 years old [old group (O-group)] and < 65 years old [young group (Y-group)]. The two groups were first compared to evaluate the distribution of the variables potentially affecting the postoperative course, including primary diagnosis, concomitant diseases, previous upper abdominal surgery, type of operation (major or minor resection), associated procedures, presence and length of portal clamping, intraoperative blood losses and transfusions, and length of operation. The outcome of hepatic resections in the two groups was comparatively evaluated in terms of postoperative mortality, morbidity, transfusions, and length of postoperative hospitalization. The Y-group included 61 resections in 60 patients, mean age 52 +/- 10 years (mean +/- SD), range 23-64 years, whereas the O-group included 44 resections in 43 patients, mean age 71 +/- 4 years (mean +/- SD ), range 65-82 years. The O-group included more hepatocellular carcinomas (45.4% vs 18.0%, P = 0.002) and chronic liver diseases (40.9% vs 18.7%, P = 0.017); the median length of operation was slightly higher in the Y-group (300 minutes vs 270 minutes, P = 0.003). Both O-group and Y-group were comparable (P = n.s.) when evaluated for all other listed variables. As far as concerns the outcome of hepatic resections in the two groups, the length of postoperative hospitalization was identical (median 9 days, 5-60 days), whereas transfusions of packed red cells (O-group vs Y-group: 25.0% vs 16.3%, P = 0.30) or fresh frozen plasma (O-group vs Y-group: 13.6% vs 6.5%, P = 0.053) were not statistically different. Postoperative mortality included one case among young patients whereas no deaths were recorded among elderly patients. Postoperative morbidity was higher in Y-group than in O-group (31.5% vs 20.5%, P = 0.59). The age factor does not negatively affect the outcome of liver resections.     

Serum apolipoprotein(a) concentrations and apo(a) phenotypes in patients with liver cirrhosis

Objective: The liver is the major site of apolipoprotein(a) synthesis, and an inverse correlation between the size of apolipoprotein(a) isoforms and its serum levels have been described. We evaluated the Apo(a) serum levels and its isoforms in patients with liver cirrhosis at different stages of the disease (Childe Turcotte classification), and during the characteristic phase of liver synthesis decline.
Methods: We studied 84 patients with liver cirrhosis and 185 control subjects with normal liver function.
Results: Apo(a) serum levels were significantly lower ( p < 0.01 ) in cirrhotic patients and, after 24 months, six patients showing a change from class A to class B had a statistically significant decrease in Apo(a) concentrations ( p = 0.0313 ). Moreover, our data showed an inversion of the small/large isoforms ratio in patient with cirrhosis in spite of the reduction in plasma concentration.
Conclusion: We showed a reduction of Apo(a) serum concentrations in a large number of patients with cirrhosis and, for the first time, during the characteristic phase of liver synthesis decline, confirming the liver as the major site of Apoliprotein(a) synthesis. Moreover we showed in the cirrhotic patients that the normal correlation between Apo(a) isoforms and Apo(a) concentrations is not conserved and the low levels are not dependent upon a high prevalence of large isoforms.     

Percutaneous vs. surgical placement of hepatic artery indwelling catheters for regional chemotherapy

BACKGROUND/AIMS: Intra-arterial hepatic chemotherapy based on floxuridine infusion is an effective treatment for hepatic metastases from colorectal cancer. The aim of the present study is the comparative analysis of surgical and percutaneous transaxillary approaches to implant a catheter into the hepatic artery for intra-arterial hepatic chemotherapy with floxuridine. METHODOLOGY: Fifty-six patients received an arterial device for intra-arterial hepatic chemotherapy. Twenty-eight patients (LPT group) underwent laparotomy to implant the catheter into the hepatic artery, the other 28 patients (PCT group) received a percutaneous catheter into the hepatic artery through a transaxillary percutaneous access. Safety and efficacy of surgical and percutaneous transaxillary approaches were comparatively analyzed in terms of number of intra-arterial hepatic chemotherapy cycles administered, device-related complications causing suppression of intra-arterial hepatic chemotherapy, and biological costs of the procedures. RESULTS: Mean postoperative hospitalization was 8.2 +/- 2.2 days in the LPT group and 1.8 +/- 0.7 days in the PCT group (P < 0.0001), while mean analgesic requirements were 9.7 +/- 3.2 doses in the LPT group and 2 +/- 0.9 doses in the PCT group (P < 0.0001). Mean number of intra-arterial hepatic chemotherapy cycles administered was 6.5 +/- 4.2 in the LPT group and 4.3 +/- 3.4 in the PCT group (P = 0.038). The overall incidence of device-related complications causing suppression of intra-arterial hepatic chemotherapy was 42.7% in the PCT group and 7.1% in the LPT group (P = 0.005). CONCLUSIONS: Surgical implantation is still recommended when laparotomy has to be performed for other contextual procedures, such as colorectal or hepatic resection, while percutaneous transaxillary catheter placement is indicated for palliative or neoadjuvant intra-arterial hepatic chemotherapy.     

Reduced severity of liver ischemia/reperfusion injury following hepatic resection in humans is associated with enhanced intrahepatic expression of Th2 cytokines.

BACKGROUND: Based on previous studies in experimental models, pro-inflammatory Th1 cytokines (i.e. TNF-alpha and IFN-gamma) are thought to play a pathogenic role in hepatic ischemia/reperfusion injury, while anti-inflammatory Th2 cytokines (i.e. IL-4 and IL-10) have been associated with reduced liver disease severity. To test the relevance of these concepts in humans, cytokine expression profiles were characterized in liver biopsies from patients undergoing hepatic resection following intermittent portal clamping. METHODS: Twelve patients were analyzed for the intrahepatic expression of TNF-alpha, IFN-gamma, IL-4 and IL-10 before and about 90min after the last reperfusion. In addition, parameters of liver damage including sALT and serum levels of TNF-alpha were analyzed at 2, 24 and 48h after surgery. RESULTS: When compared with pre-reperfusion liver specimens, all post-reperfusion biopsies showed significantly increased levels of TNF-alpha and IFN-gamma mRNAs. Conversely IL-4 and IL-10 mRNA levels were significantly increased in only seven patients. A negative correlation was observed between Th2 cytokines (IL-4, IL-10) and ALT and serum levels of TNF-alpha. Furthermore, the presence of hepatic steatosis was significantly associated with lower intrahepatic contents of IL-4 and IL-10. CONCLUSIONS: The results suggest that the local early expression of Th2 cytokines may contribute to attenuate liver injury following ischemia reperfusion in humans. The early imbalance between pro- and anti-inflammatory cytokines seen in steatotic liver subjected to I/R could explain, at least partially, the decreased tolerance of steatotic livers to I/R injury.     

Cortical Astrocyte-neuronal Metabolic Coupling Emerges as a Critical Modulator of Stress-induced Hopelessness

Stress is a major risk factor for the development of mental illness,such as major depression disorder (MDD)[1].Despite decades of progress,including findings that stressinduced depression corresponds with numerous morphological and functional neuronal changes within brain structures associated with cognition and mood,such as the medial prefrontal cortex (mPFC)[1-3],a thorough understanding of how stress induces the core symptoms of depression,such as hopelessness,is still lacking.In an exciting new paper in mice,Yin et al.show that astrocyteneuronal metabolic coupling in the mPFC is critically involved in the stress-induced passive coping response in mice [4].     

Mercury occurrence in Italian seafood from the Mediterranean Sea and possible intake scenarios of the Italian coastal population

Mercury (Hg) settlements in the Mediterranean Sea determine a potential toxicological relevance of seafood intakes for coastal populations. To assess this possibility, fish, molluscs, and crustaceans of commercial size of 69 different species were sampled and analyzed for total mercury (Hg_TOT) from georeferenced areas and evaluated for their compliance with the European Union Maximum Residue Limits of 0.5 and 1.0 mg/kg wet weight (ww). Accounting for the weekly estimated seafood intake in the Italian coastal population (mean 469–626 g/person/week) it was then possible to recover threshold contamination values in seafood. Under a Tolerable Weekly Intake of 1.3 μg/kg/bw/week, a threshold seafood contamination <0.10 mg/kg ww has been derived for sensitive groups. A suitable algorithm based on the parallel MeHg and Hg_TOT analysis on the most consumed species, helped to refine the uncertainties related to the conservative assumption in seafood all the Hg_TOT present is in form of MeHg. This work aims to improve the link between the risk management and risk assessment strategies, with the identification of those fish and seafood species, that, when regularly consumed, could determine or prevent potential Hg_TOT/MeHg overintakes in sensitive groups.