Major liver resections, perioperative issues and posthepatectomy liver failure: A comprehensive update for the anesthesiologist.

Significant advances in surgical techniques and relevant medium- and long-term outcomes over the past two decades have led to a substantial expansion in the indications for major liver resections. To support these outstanding results and to reduce perioperative complications, anesthesiologists must address and master key perioperative issues (preoperative assessment, proactive intraoperative anesthesia strategies, and implementation of the Enhanced Recovery After Surgery approach). Intensive care unit monitoring immediately following liver surgery remains a subject of active and often unresolved debate. Among postoperative complications, posthepatectomy liver failure (PHLF) occurs in different grades of severity (A-C) and frequency (9%-30%), and it is the main cause of 90-d postoperative mortality. PHLF, recently redefined with pragmatic clinical criteria and perioperative scores, can be predicted, prevented, or anticipated. This review highlights: (1) The systemic consequences of surgical manipulations anesthesiologists must respond to or prevent, to positively impact PHLF (a proactive approach); and (2) the maximal intensive treatment of PHLF, including artificial options, mainly based, so far, on Acute Liver Failure treatment(s), to buy time waiting for the recovery of the native liver or, when appropriate and in very selected cases, toward liver transplant. Such a clinical context requires a strong commitment to surgeons, anesthesiologists, and intensivists to work together, for a fruitful collaboration in a mandatory clinical continuum.

Liver Transplantation and the Elderly Candidate: Perioperative Considerations.

Pioneered by Thomas Starzl in the early 1970s, liver transplant (LT) is nowadays often considered a final intervention and standard of care to cure many forms of acute and chronic end-stage liver diseases. Started in recipients younger than 60 years old, LT indications are now much broader, and at least, one-fifth of the candidates are older than 65 years. Problems associated with ageing and frailty in LT recipients and their impact on the entire perioperative course are discussed according to a modern anesthesiological perspective and the anesthesiologist covering the role of the perioperative (transplant) physician.

Preoperative cardiac assessment in liver transplant candidates.

New and extended indications, older age, higher cardiovascular risk, and the long-standing cirrhosis-associated complications mandate specific skills for an appropriate preoperative assessment of the liver transplant (LT) candidate. The incidence of cardiac diseases (dysrhythmias, cardiomyopathies, coronary artery disease, valvular heart disease) are increasing among LT recipients: however, no consensus exists among clinical practice guidelines for cardiovascular screening and risk stratification. In spite of different "transplant center-centered protocols", basic "pillars" are common (electrocardiography, baseline echocardiography, functional assessment). Owing to intrinsic limitations, yields and relevance of noninvasive stress tests, under constant scrutiny even if used, are discussed, focusing the definition of the "high risk" candidate and exploring noninvasive imaging and new forms of stress imaging. The aim is to find an appropriate and rational stepwise algorithm. The final commitment is to select the right candidate for a finite resource, the graft, able to save (and change) lives.

Oxidative inhibition of protein phosphatase 2A activity: role of catalytic subunit disulfides.

A molecular basis for the inhibition of brain protein phosphatase 2A (PP2A) activity by oxidative stress was examined in a high-speed supernatant (HSS) fraction from rat cerebral cortex. PP2A activity was subject to substantial disulfide reducing agent-reversible inhibition in the HSS fraction. Results of gel electrophoresis support the conclusions that inhibition of PP2A activity was associated with the both the disulfide cross-linking of the catalytic subunit (PP2A(C)) of the enzyme to other brain proteins and with the formation of an apparent novel intramolecular disulfide bond in PP2A(C). Additional findings that the vicinal dithiol cross-linking reagent phenylarsine oxide (PAO) produced a potent dithiothreitol-reversible inhibition of PP2A activity suggest that the cross-linking of PP2A(C) vicinal thiols to form an intramolecular disulfide bond may be sufficient to inhibit PP2A activity under oxidative stress. We propose that the dithiol-disulfide equilibrium of a vicinal thiol pair of PP2A(C) may confer redox sensitivity on cellular PP2A.