Diagnostic criteria and severity assessment of acute cholecystitis: Tokyo Guidelines

The aim of this article is to propose new criteria for the diagnosis and severity assessment of acute cholecystitis, based on a systematic review of the literature and a consensus of experts. A working group reviewed articles with regard to the diagnosis and treatment of acute cholecystitis and extracted the best current available evidence. In addition to the evidence and face-to-face discussions, domestic consensus meetings were held by the experts in order to assess the results. A provisional outcome statement regarding the diagnostic criteria and criteria for severity assessment was discussed and finalized during an International Consensus Meeting held in Tokyo 2006. Patients exhibiting one of the local signs of inflammation, such as Murphy’s sign, or a mass, pain or tenderness in the right upper quadrant, as well as one of the systemic signs of inflammation, such as fever, elevated white blood cell count, and elevated C-reactive protein level, are diagnosed as having acute cholecystitis. Patients in whom suspected clinical findings are confirmed by diagnostic imaging are also diagnosed with acute cholecystitis. The severity of acute cholecystitis is classified into three grades, mild (grade I), moderate (grade II), and severe (grade III). Grade I (mild acute cholecystitis) is defined as acute cholecystitis in a patient with no organ dysfunction and limited disease in the gallbladder, making cholecystectomy a low-risk procedure. Grade II (moderate acute cholecystitis) is associated with no organ dysfunction but there is extensive disease in the gallbladder, resulting in difficulty in safely performing a cholecystectomy. Grade II disease is usually characterized by an elevated white blood cell count; a palpable, tender mass in the right upper abdominal quadrant; disease duration of more than 72 h; and imaging studies indicating significant inflammatory changes in the gallbladder. Grade III (severe acute cholecystitis) is defined as acute cholecystitis with organ dysfunction

Intermittent Ischemia but Not Ischemic Preconditioning Is Effective in Restoring Bile Flow After Ischemia Reperfusion Injury in the Livers of Aged Rats

BackgroundlAims. Ischemic preconditioning (IPC) and intermittent ischemia (INT) reduce liver injury following ischemia reperfusion in liver resections. Aged livers are at higher risk for ischemia reperfusion injury, but little is known of the effectiveness of IPC and INT in aged livers. The aim of this study was to investigate the effects of IPC and INT on ischemia reperfusion injury in aged livers. Methods. A rat model of segmental hepatic ischemia (45 min) and reperfusion (60 min) was used. Bile flow, as an indicator of early hepatocyte damage and dynamic liver function, plasma concentrations of bilirubin, liver marker enzymes, and liver histology were assessed. Results. In young rats (8-13 weeks), IPC regimes of 10 min clamping and 10 min reperfusion, and 5 min clamping and 30 min reperfusion, restored bile flow to 23 and 42%, respectively, of the initial value, compared to 14 and 88% for continuous clamping and controls, respectively. An M regime of three cycles of alternating 15 min perfusion and 15 min clamping gave a substantially greater (70%) restoration of bile flow. In aged rats (20-24 months), the IPC regimes did not give any restoration of bile flow. By contrast, the INT regime restored bile flow to 68%. Plasma bilirubin concentrations were lowest in the INT groups, whereas alanine transaminase concentrations for the IPC and INT groups compared with the continuous clamping groups showed no significant differences. Conclusions. In young rats, INT is more effective than IPC in restoring the immediate consequences of IP-induced damage to hepatocytes and liver function after ischemia-reperfusion. In aged rats INT, but not IPC, reverses hepatocyte damage and restores liver function. INT may promote better hepatocyte and liver function than IPC following the surgical resection of aged livers. (c) 2009 Elsevier Inc. All rights reserved

Intermittent ischemia enhances the uptake of indocyanine green to livers subject to ischemia and reperfusion

Background and Aim: Intermittent ischemia is known to promote post perfusion bile flow, and hence recovery of liver function following ischemia reperfusion of the liver. However, the mechanisms involved are not well understood. The aim of this study was to identify the step(s) in the bile acid transport pathway altered by intermittent ischemia. Methods: Arat model of segmental hepatic ischemia in which the bilateral median and left lateral lobes were made ischemic by clamping the blood vessels was used. Indocyanine green (ICG), infrared spectroscopy, and compartmental kinetic analysis, were used to indirectly monitor the movement of bile acids across hepatocytes in situ. Rates of bile flow were measured gravimetrically. Results: In control livers (not subjected to ischemia), the movement of ICG from the blood to bile fluid could be described by a three compartment model comprising the blood, a rapidly-exchangeable compartment, and the hepatocyte cytoplasmic space. In livers subjected to continuous clamping, the rates of ICG uptake to the liver, and outflow from the liver, were greatly reduced compared with those in control livers. Intermittent clamping (three episodes of 15 min clamping) compared with continuous clamping substantially increased the rate of ICG uptake from the blood but had less effect on the rate of ICG outflow from hepatocytes. Conclusions: It is concluded that intermittent ischemia promotes post reperfusion bile flow in the early phase of ischemia reperfusion injury principally by enhancing the movement of bile acids from the blood to hepatocytes

Increased expression of peroxiredoxin 1 and identification of a novel lipid-metabolizing enzyme in the early phase of liver ischemia reperfusion injury

Warm ischemia reperfusion (IR) injury of the liver is associated with changes in the expression and/or post-translational modification of numerous proteins. Only a few of these have been identified. We used 2-D DIGE to identify cytosolic proteins altered in the early stage of IR in an established rat model of segmental hepatic ischemia. Proteins in 18 abundant spots altered by IR were identified by LC-MS/MS and Western blot. Many identified proteins were enzymes involved in glucose and lipid metabolism. Isoamyl acetate-hydrolysing esterase 1 homolog, not previously characterized in liver, was also identified. A threefold increase in peroxiredoxin 1 (Prx1) and its oxidized forms was observed as was an increase in Prx1 mRNA. Peroxiredoxins and their overoxidation have previously been associated with IR. In contrast to other studies, we did not detect typical overoxidation of Prx1 on the peroxidatic cysteine (Cys(52)). Instead, we identified novel overoxidation of the resolving cysteine (Cys(173)) residue by LC-MS/MS. Our results show that a rapid increase in Prx1 expression is associated with the early phase of IR of the liver, likely contributing to mechanisms that protect the liver against IR damage. Additionally, we have revealed a potential role in liver for a novel lipid-metabolizing enzyme

Rapamycin Induces Heme Oxygenase-1 in Liver but Inhibits Bile Flow Recovery after Ischemia

Background/Aims. Rapamycin, which is employed in the management of patients undergoing liver surgery, induces the synthesis of heme oxygenase-1 (HO-1) in some non-liver cell types. The aim was to investigate whether rapamycin can induce HO-1 expression in the liver, and to test the effects of rapamycin on liver function in the early phase of ischemia reperfusion (IR) injury. Methods. Isolated rat hepatocytes and a rat model of segmental hepatic ischemia and reperfusion were employed. Bile flow was measured gravimetrically or by using indocyanine green. mRNA and protein (by quantitative PCR and Western blot, respectively) and blood concentrations of rapamycin, bilirubin, and liver marker enzymes were measured. Results. In isolated hepatocytes, rapamycin induced a 6-fold increase in HO-1, comparable to that induced by cobalt proporphyrin (CoPP), and a 2-fold increase in peroxiredoxin-1. Pretreatment of rats with rapamycin resulted in a small increase in liver HO-1 expression, a 20% inhibition of the basal rate of bile flow, and a 50% inhibition in the rate of bile flow recovery after ischemia. CoPP increased basal bile flow by 20% and inhibited bile flow recovery by 50%. These effects were associated with small increases in the blood concentrations of bilirubin and liver marker enzymes. Conclusions. Rapamycin, through HO-1 induction, has the potential to protect the liver against damage in the late phase of IR. The inhibition by rapamycin of bile flow indicates that its actions on liver function in the acute phase of IR injury are complex. (C) 2012 Elsevier Inc. All rights reserved

Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury

Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood. Objective. The aim was to investigate this question. Material and methods. A rat model of segmental hepatic ischemia was employed. Rats were pre-treated with the estrogen receptor antagonist ICI182,780 and/or the estrogen receptor agonist 17 beta-estradiol. Bile flow, blood concentrations of bilirubin and liver enzymes were measured, and liver histology was assessed. Results. Bile flow recovery immediately after the initiation of reperfusion was faster in females than in males. ICI182,780 reduced the rate of bile flow recovery in females but this reduction was not reversed by co-administration of 17 beta-estradiol. In males, 17 beta-estradiol alone did not enhance bile flow recovery. The changes in bile flow recovery observed under a given condition were correlated with small changes in blood liver enzymes and liver histology. Conclusions. Sex has a significant influence on the early recovery of liver function in the acute phase of IR injury. However, in female rats estrogen receptors play only a limited role in mediating enhanced recovery of liver function.</p

Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury

Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood. Objective. The aim was to investigate this question. Material and methods. A rat model of segmental hepatic ischemia was employed. Rats were pre-treated with the estrogen receptor antagonist ICI182,780 and/or the estrogen receptor agonist 17 beta-estradiol. Bile flow, blood concentrations of bilirubin and liver enzymes were measured, and liver histology was assessed. Results. Bile flow recovery immediately after the initiation of reperfusion was faster in females than in males. ICI182,780 reduced the rate of bile flow recovery in females but this reduction was not reversed by co-administration of 17 beta-estradiol. In males, 17 beta-estradiol alone did not enhance bile flow recovery. The changes in bile flow recovery observed under a given condition were correlated with small changes in blood liver enzymes and liver histology. Conclusions. Sex has a significant influence on the early recovery of liver function in the acute phase of IR injury. However, in female rats estrogen receptors play only a limited role in mediating enhanced recovery of liver function

Surgery Triage during the COVID-19 Pandemic

Background: The novel coronavirus, SARS‐CoV‐2, caused the COVID‐19 global pandemic. In response, the Australian and New Zealand governments activated their respective emergency plans and hospital frameworks to deal with the potential increased demand on scarce resources. Surgical triage formed an important part of this response to protect the healthcare system’s capacity to respond to COVID‐19. Method: A rapid review methodology was adapted to search for all levels of evidence on triaging surgery during the current COVID‐19 outbreak. Searches were limited to PubMed (inception to 10 April 2020) and supplemented with grey literature searches using the Google search engine. Further, relevant articles were also sourced through the RACS COVID‐19 Working Group. Recent government advice (May 2020) is also included. Results: This rapid review is a summary of advice from Australian, New Zealand and international speciality groups regarding triaging of surgical cases, as well as the peer‐reviewed literature. The key theme across all jurisdictions was to not compromise clinical judgment and to enable individualised, ethical and patient‐centred care. The topics reported on include implications of COVID‐19 on surgical triage, competing demands on healthcare resources (surgery versus COVID‐19 cases), and the low incidence of COVID‐19 resulting in a possibility to increase surgical caseloads over time. Conclusion: During the COVID‐19 pandemic, urgent and emergency surgery must continue. A carefully staged return of elective surgery should align with a decrease in COVID‐19 caseload. Combining evidence and expert opinion, schemas and recommendations have been proposed to guide this process in Australia and New Zealand