/pdf/nccn-clinical-practice-guidelines-in-oncology-hepatobiliary-1kpacqqvi8.pdf

NCCN clinical practice guidelines in oncology: hepatobiliary cancers.

BACKGROUND: Concerns regarding the safety of transfused blood have led to the development of a range of interventions to minimise blood loss during major surgery. Anti-fibrinolytic drugs are widely used, particularly in cardiac surgery, and previous reviews have found them to be effective in reducing blood loss, the need for transfusion, and the need for re-operation due to continued or recurrent bleeding. In the last few years questions have been raised regarding the comparative performance of the drugs. The safety of the most popular agent, aprotinin, has been challenged, and it was withdrawn from world markets in May 2008 because of concerns that it increased the risk of cardiovascular complications and death. OBJECTIVES: To assess the comparative effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) on blood loss during surgery, the need for red blood cell (RBC) transfusion, and adverse events, particularly vascular occlusion, renal dysfunction, and death. SEARCH STRATEGY: We searched: the Cochrane Injuries Group's Specialised Register (July 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 3), MEDLINE (Ovid SP) 1950 to July 2010, EMBASE (Ovid SP) 1980 to July 2010. References in identified trials and review articles were checked and trial authors were contacted to identify any additional studies. The searches were last updated in July 2010. SELECTION CRITERIA: Randomised controlled trials (RCTs) of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. Eligible trials compared anti-fibrinolytic drugs with placebo (or no treatment), or with each other. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: This review summarises data from 252 RCTs that recruited over 25,000 participants. Data from the head-to-head trials suggest an advantage of aprotinin over the lysine analogues TXA and EACA in terms of reducing perioperative blood loss, but the differences were small. Compared to control, aprotinin reduced the probability of requiring RBC transfusion by a relative 34% (relative risk [RR] 0.66, 95% confidence interval [CI] 0.60 to 0.72). The RR for RBC transfusion with TXA was 0.61 (95% CI 0.53 to 0.70) and was 0.81 (95% CI 0.67 to 0.99) with EACA. When the pooled estimates from the head-to-head trials of the two lysine analogues were combined and compared to aprotinin alone, aprotinin appeared more effective in reducing the need for RBC transfusion (RR 0.90; 95% CI 0.81 to 0.99).Aprotinin reduced the need for re-operation due to bleeding by a relative 54% (RR 0.46, 95% CI 0.34 to 0.62). This translates into an absolute risk reduction of 2% and a number needed-to-treat (NNT) of 50 (95% CI 33 to 100). A similar trend was seen with EACA (RR 0.32, 95% CI 0.11 to 0.99) but not TXA (RR 0.80, 95% CI 0.55 to 1.17). The blood transfusion data were heterogeneous and funnel plots indicate that trials of aprotinin and the lysine analogues may be subject to publication bias.When compared with no treatment aprotinin did not increase the risk of myocardial infarction (RR 0.87, 95% CI 0.69 to 1.11), stroke (RR 0.82, 95% CI 0.44 to 1.52), renal dysfunction (RR 1.10, 95% CI 0.79 to 1.54) or overall mortality (RR 0.81, 95% CI 0.63 to 1.06). Similar trends were seen with the lysine analogues, but data were sparse. These data conflict with the results of recently published non-randomised studies, which found increased risk of cardiovascular complications and death with aprotinin. There are concerns about the adequacy of reporting of uncommon events in the small clinical trials included in this review.When aprotinin was compared directly with either, or both, of the two lysine analogues it resulted in a significant increase in the risk of death (RR 1.39, 95% CI 1.02, 1.89), and a non-significant increase in the risk of myocardial infarction (RR 1.11 95% CI 0.82, 1.50). Most of the data contributing to this added risk came from a single study - the BART trial (2008). AUTHORS' CONCLUSIONS: Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the receipt of allogeneic red cell transfusion. Aprotinin appears to be slightly more effective than the lysine analogues in reducing blood loss and the receipt of blood transfusion. However, head to head comparisons show a lower risk of death with lysine analogues when compared with aprotinin. The lysine analogues are effective in reducing blood loss during and after surgery, and appear to be free of serious adverse effects.

/pdf/anti-fibrinolytic-use-for-minimising-perioperative-2mv3d62q1l.pdf

Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion

The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient’s tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

https://epub.ub.uni-muenchen.de/24023/1/oa_24023.pdf

Management of severe perioperative bleeding Guidelines from the European Society of Anaesthesiology

BACKGROUND: Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. METHODS: We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first- and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. RESULTS: Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P=0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAi-mediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. CONCLUSIONS: ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov numbers, NCT01148953 and NCT01559077.).

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1208760

Safety and efficacy of RNAi therapy for transthyretin amyloidosis

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.26972

Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

BACKGROUND

Transcatheter arterial chemoembolization (TACE) has been used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its prognostic usefulness has not previously been clarified.



METHODS

The authors reviewed all patients treated at their institution with TACE for unresectable HCC in order to analyze prognostic factors and to determine which patients might benefit from this treatment. One hundred forty-three patients were retrospectively studied. Pretreatment, treatment, and follow-up variables with possible prognostic significance were analyzed. A stepwise multivariate analysis was performed using the Cox regression model, and a prognostic index was obtained.



RESULTS

According to univariate analysis, variables significantly associated with survival were α-fetoprotein (>400 U/L), tumor size (>50%), ascites, albumin ( 400 U/L), tumor size (>50%), Child–Pugh grade (Child C), pattern of iodized oil uptake, and portal vein thrombosis were independent factors in multivariate analysis. Using the β-coefficients of α-fetoprotein (>400 U/L), tumor size (>50%) and Child–Pugh score, a prognostic index was calculated, and according to this index patients were classified into 3 categories with different prognoses. Ascites was excluded from the analysis because it is included in Child–Pugh grade, and iodized oil uptake was excluded because it cannot be evaluated before treatment.



CONCLUSIONS

This simple prognostic index can predict the survival of patients treated with TACE and can therefore be used to decide which patients with unresectable HCC should receive this therapy. TACE should not be administered to patients with one or more positive prognostic factors. Cancer 2000;88:50–7. © 2000 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/%28SICI%291097-0142%2820000101%2988%3A1%3C50%3A%3AAID-CNCR8%3E3.0.CO%3B2-I

A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization.

UNLABELLED We evaluated the efficacy of the prophylactic administration of epsilon-aminocaproic acid and tranexamic acid for reducing blood product requirements in orthotopic liver transplantation (OLT) in a prospective, double-blinded study performed in 132 consecutive patients. Patients were randomized to three groups and given one of three drugs prophylactically: tranexamic acid, 10 mg. kg(-1). h(-1); epsilon-aminocaproic acid, 16 mg. kg(-1). h(-1), and placebo (isotonic saline). Perioperative management was standardized. Coagulation tests, thromboelastogram, and blood requirements were recorded during OLT and in the first 24 h. There were no differences in diagnosis, Child score, or preoperative coagulation tests among groups. Administration of packed red blood cells was significantly reduced (P = 0.023) during OLT in the tranexamic acid group, but not in the epsilon-aminocaproic acid group. There were no differences in transfusion requirements after OLT. Thromboembolic events, reoperations, and mortality were similar in the three groups. Prophylactic administration of tranexamic acid, but not epsilon-aminocaproic acid, significantly reduces total packed red blood cell usage during OLT. IMPLICATIONS In a randomized study of 132 consecutive patients undergoing liver transplantation, we found that tranexamic acid, but not epsilon-aminocaproic acid, reduced intraoperative total packed red blood cell transfusion.

Tranexamic acid reduces red cell transfusion better than epsilon-aminocaproic acid or placebo in liver transplantation.

Background:  Splanchnic thrombosis is a surgical challenge in liver transplantation (LT). The aim of this study was to analyze our experience in the management of portal vein thrombosis, and its influence on evolution.



Aim:  The aim of this study was to analyze our experience in the management of portal vein thrombosis, and its influence on evolution.



Patients and methods:  Between 1999 and 2004, 366 liver transplants were performed in 335 patients. Forty-two patients [12.5%: portal vein thrombosis (PVT) group] had portal thrombosis at the time of LT. We analyzed the technical aspects and compared their evolution with a group of patients without portal thrombosis (n = 293; no-PVT group). Retransplantations were excluded.



Results:  Of the 42 patients with thrombosis, 18 had partial thrombosis and 16 complete thrombosis [six included the proximal superior mesenteric vein (SMV) and in two the whole splanchnic system]. In 12 cases, usual T-T anastomosis was performed and in 16 cases a thrombectomy was carried out; there were five cases of anastomosis at confluence of the SMV, five cases of anastomosis to a collateral vein, three cases of venous graft, and one case of cavoportal hemitransposition. The operative time was higher in PVT group (417 ± 103 min vs. 363 ± 83; p = 0.0005), as RBC transfusion (2.4 ± 3.1 vs. 1.9 ± 2.3; p = 0.04), and hospital stay (20.9 ± 14.9 d vs. 15.1 ± 10.6; p = 0.002). However, there were no differences in hospital mortality (4% vs. 7.8%; p = 0.98), primary dysfunction (4.8% vs. 7.8%; p = 0.44), or three-yr-actuarial survival (75% vs. 77%; p = 0.95). The incidence of post-transplant thrombosis was higher in the PVT group (15% vs. 2.4%; p = 0.0005).



Conclusions:  Portal thrombosis is associated with greater operative complexity and rethrombosis, but has no influence on overall morbidity and mortality.

Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality.

https://www.journal-of-hepatology.eu/article/S0168-8278(06)00006-7/pdf

Immunosuppression without steroids in liver transplantation is safe and reduces infection and metabolic complications: Results from a prospective multicenter randomized study ☆

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/lt.20075

Antoni Rafecas

Papers

A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization.

Tranexamic acid reduces red cell transfusion better than epsilon-aminocaproic acid or placebo in liver transplantation.

Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality.

Immunosuppression without steroids in liver transplantation is safe and reduces infection and metabolic complications: Results from a prospective multicenter randomized study ☆

The Prophylactic Use of Tranexamic Acid and Aprotinin in Orthotopic Liver Transplantation: A Comparative Study