Beyond Preconditioning: Postconditioning as an Alternative Technique in the Prevention of Liver Ischemia-Reperfusion Injury

Liver ischemia/reperfusion injury may significantly compromise hepatic postoperative function. Various hepatoprotective methods have been improvised, aiming at attenuating IR injury. With ischemic preconditioning (IPC), the liver is conditioned with a brief ischemic period followed by reperfusion, prior to sustained ischemia. Ischemic postconditioning (IPostC), consisting of intermittent sequential interruptions of blood flow in the early phase of reperfusion, seems to be a more feasible alternative than IPC, since the onset of reperfusion is more predictable. Regarding the potential mechanisms involved, it has been postulated that the slow intermittent oxygenation through controlled reperfusion decreases the burst production of oxygen free radicals, increases antioxidant activity, suppresses neutrophil accumulation, and modulates the apoptotic cascade. Additionally, favorable effects on mitochondrial ultrastructure and function, and upregulation of the cytoprotective properties of nitric oxide, leading to preservation of sinusoidal structure and maintenance of blood flow through the hepatic circulation could also underlie the protection afforded by postconditioning. Clinical studies are required to show whether biochemical and histological improvements afforded by the reperfusion/reocclusion cycles of postconditioning during early reperfusion can be translated to a substantial clinical benefit in liver resection and transplantation settings or to highlight more aspects of its molecular mechanisms

Global Consequences of Liver Ischemia/Reperfusion Injury

Liver ischemia/reperfusion injury has been extensively studied during the last decades and has been implicated in the pathophysiology of many clinical entities following hepatic surgery and transplantation. Apart from its pivotal role in the pathogenesis of the organ’s post reperfusion injury, it has also been proposed as an underlying mechanism responsible for the dysfunction and injury of other organs as well. It seems that liver ischemia and reperfusion represent an event with “global” consequences that influence the function of many remote organs including the lung, kidney, intestine, pancreas, adrenals, and myocardium among others. The molecular and clinical manifestation of these remote organs injury may lead to the multiple organ dysfunction syndrome, frequently encountered in these patients. Remote organ injury seems to be in part the result of the oxidative burst and the inflammatory response following reperfusion. The present paper aims to review the existing literature regarding the proposed mechanisms of remote organ injury after liver ischemia and reperfusion

Two Cases of Primary Splenic Hydatid Cyst in Greece

Cystic disease of the spleen is an uncommon entity in general population. Most cases result from parasitic infection by Echinococcus granulosus, a form called splenic hydatid disease (SHD), with a reported frequency of 0.5-6.0% within abdominal hydatidosis. On the contrary, an isolated splenic involvement of hydatid disease is very uncommon even in endemic regions. Two cases of primary SHD managed with open and laparoscopic radical surgery in our department are reported herein. Primary SHD is a rare entity with non-specific symptoms underlying clinical suspicion by the physician for prompt diagnosis. Surgical treatment is the mainstay therapy, while laparoscopic approach when feasible is safe, offering the advantages of laparoscopic surgery

Outcomes of Different Quality of Life Assessment Modalities After Breast Cancer Therapy : A Network Meta-analysis

Funding/Support: This study was supported by funding from the NHS Grampian Endowment Fund (Mr Masannat).Peer reviewedPublisher PD

Nitrosative and Oxidative Stresses Contribute to Post-Ischemic Liver Injury Following Severe Hemorrhagic Shock: The Role of Hypoxemic Resuscitation

Purpose: Hemorrhagic shock and resuscitation is frequently associated with liver ischemia-reperfusion injury. The aim of the study was to investigate whether hypoxemic resuscitation attenuates liver injury. Methods: Anesthetized, mechanically ventilated New Zealand white rabbits were exsanguinated to a mean arterial pressure of 30 mmHg for 60 minutes. Resuscitation under normoxemia (Normox-Res group, n = 16, PaO2 = 95–105 mmHg) or hypoxemia (Hypox-Res group, n = 15, PaO 2 = 35–40 mmHg) followed, modifying the FiO 2. Animals not subjected to shock constituted the sham group (n = 11, PaO 2 = 95–105 mmHg). Indices of the inflammatory, oxidative and nitrosative response were measured and histopathological and immunohistochemical studies of the liver were performed. Results: Normox-Res group animals exhibited increased serum alanine aminotransferase, tumor necrosis factor- alpha, interleukin (IL)-1b and IL-6 levels compared with Hypox-Res and sham groups. Reactive oxygen species generation, malondialdehyde formation and myeloperoxidase activity were all elevated in Normox-Res rabbits compared with Hypox-Res and sham groups. Similarly, endothelial NO synthase and inducible NO synthase mRNA expression was up-regulated and nitrotyrosine immunostaining increased in animals resuscitated normoxemically, indicating a more intense nitrosative stress. Hypox-Res animals demonstrated a less prominent histopathologic injury which was similar to sham animals. Conclusions: Hypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory respons

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Hypoxemic resuscitation from hemorrhagic shock: an experimental study on the involved basic mechanisms

The present study was designed to investigate whether serum ofanimals subjected to hypoxemic resuscitation from haemorrhagic shock maybe a weak stimulant for monocytes or not. Twenty rabbits were subjected tohaemorrhagic shock after blood exsanguination; resuscitation was performedby infusion of the shed blood in eight rabbits under normoxemic conditions(NormoxRes) and in twelve under hypoxemic conditions (HypoxRes); sevenrabbits were subjected to sham operation. Malondialdehyde (MDA) andtumour necrosis factor (TNF)-a levels were estimated in serum at serial timeintervals; the serum was applied for stimulation of U937 monocytes with orwithout the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580.Expression of triggering receptor expressed on myeloid cells-1 (TREM-1) onU937 was also assessed by flow cytometric analysis. Death supervened infour animals of the NormoxRes (50%) and in one animal of the HypoxResgroup (8·33%, P: 0·032). Serum levels of TNF-a and MDA were higher inNormoxRes compared to HypoxRes animals. Expression of TREM-1 on U937monocytes was similar after stimulation with serum sampled from bothgroups. Concentrations of interleukin (IL)-1b, IL-6 and IL-8 of monocytessupernatants were higher after stimulation with serum of NormoxRes thanHypoxRes rabbits. Production of cytokines after stimulation with serum wasdecreased significantly after addition of SB203580. It is concluded thatstimulation of monocytes may contribute to the generation of the systemicinflammatory response during reperfusion after ischemia. Lower stimulation ofthe p38 MAPK-mediated production of IL-1b, IL-6 and IL-8 by monocytes may112be implicated as an explanation for the benefits shown for the host whenresuscitation is performed under hypoxemic conditionsΣκοπός της παρούσας εργασίας ήταν να μελετήσουμε την επίδρασητης υποξαιμικής ανάταξης του αιμορραγικού shock στη διέγερση τωνμονοκυττάρων και στην επακόλουθη συστηματική φλεγμονώδη απάντηση. Τουλικό της μελέτης αποτέλεσαν είκοσι επτά κόνικλοι. Είκοσι εξ αυτών,υποβλήθηκαν σε αιμορραγικό shock μέσω αφαίμαξης. Ακολούθησε ανάταξη ηοποία πραγματοποιήθηκε μέσω της χορήγησης του προηγούμενασυλλεγχθέντος αίματος υπό συνθήκες νορμοξαιμίας (ομάδα NormoxRes) σεοκτώ κόνικλους και υπό συνθήκες υποξαιμίας (ομάδα HypoxRes) σε δώδεκακόνικλους. Οι υπόλοιποι επτά κόνικλοι αποτέλεσαν την ομάδα ελέγχου(ομάδα Sham), οι οποίοι υποβλήθηκαν σε όλους τους πειραματικούςχειρισμούς με εξαίρεση την αφαίμαξη. Ο ορός των πειραματοζώων σεδιάφορες χρονικές στιγμές χρησίμευσε για τον προσδιορισμό δεικτών τουοξειδωτικού και φλεγμονώδους stress όπως η μαλονδιαλδεϋδη (MDA) και οπαράγοντας νέκρωσης των όγκων – α (Tumor Necrosis Factor TNF - α).Ακολούθως ο ορός από τα πειραματόζωα χρησιμοποιήθηκε για τη διέγερσητων μονοκυττάρων της σειράς U937 με και χωρίς την παρουσία τουπαράγοντα SB203580 ο οποίος είναι αναστολέας της p38 MAP κινάσης.Επίσης μετρήθηκε με τη χρήση κυτταρομετρίας ροής η έκφραση TREM-1(triggering receptor expressed on Myeloid cells-1). Τέσσερα ζώα από τηνομάδα NormoxRes (ποσοστό 50%) και ένα ζώο από την αμάδα HypoxRes(ποσοστό 8,33%, P=0,032) πέθαναν. Τα επίπεδα του TNF - α και της MDAήταν υψηλότερα στον ορό των ζώων της ομάδας NormoxRes συγκριτικά μετην ομάδα Hypox-Res. Η έκφραση του TREM-1 στα μονοκύτταρα της σειράςU937 ήταν παρόμοια μετά διέγερση με ορό και από τις δύο ομάδες110πειραματοζώων. Οι συγκεντρώσεις των ιντερλευκινών IL-1β, IL-6 και IL-8 σταυπερκείμενα των μονοκυττάρων ήταν υψηλότερες μετά διέγερση με ορό απότους κόνικλους της ομάδας NormoxRes σε σχέση με την ομάδα HypoxRes. Ηπαραγωγή των κυτταροκινών μειώθηκε σημαντικά μετά την προσθήκη τουSB203580. Συμπερασματικά θα μπορούσε να υποστηριχτεί ότι η διέγερσητων μονοκυττάρων μπορεί να συμβάλλει στην επαγόμενη συστηματικήφλεγμονώδη απάντηση λόγω του συνδρόμου ισχαιμίας – επαναιμάτωσης. Ημικρότερη παραγωγή των IL-1β, IL-6 και IL-8 από τα μονοκύτταρα, η οποίαδιαμεσολαβείται μέσω του μονοπατιού της p38 MAP κινάσης θα μπορούσε ναθεωρηθεί ως μια εξήγηση για την ευνοϊκή επίδραση της υποξαιμικής ανάταξηςτου αιμορραγικού shock