In-hospital survival after pancreatoduodenectomy is greater in high-volume hospitals versus lower-volume hospitals: a meta-analysis.

BACKGROUND: Variation in cut-off values for what is considered a high volume (HV) hospital has made assessments of volume-outcome relationships for pancreaticoduodenectomy (PD) challenging. Accordingly, we performed a systematic review and meta-analysis comparing in-hospital mortality after PD in hospitals above and below HV thresholds of various cut-off values. METHOD: PubMed/MEDLINE, Embase and Cochrane Library were searched to 4 January 2021 for studies comparing in-hospital mortality after PD in hospitals above and below defined HV thresholds. After data extraction, risk of bias was assessed using the Downs and Black checklist. A random-effects model was used for meta-analysis, including meta-regressions. Registration: PROSPERO, CRD42021224432. RESULTS: From 1855 records, 17 observational studies of moderate quality were included. Median HV cut-off was 25 PDs/year (IQR: 20-32). Overall relative risk of in-hospital mortality was 0.37 (95% CI: 0.30, 0.45), that is, 63% less in HV hospitals. All subgroup analyses found an in-hospital survival benefit in performing PDs at HV hospitals. Meta-regressions from included studies found no statistically significant associations between relative risk of in-hospital mortality and region (USA vs. non-USA; p = 0.396); or 25th percentile (p = 0.231), median (p = 0.822) or 75th percentile (p = 0.469) HV cut-off values. Significant inverse relationships were found between PD hospital volume and other outcomes. CONCLUSION: In-hospital survival was significantly greater for patients undergoing PDs at HV hospitals, regardless of HV cut-off value or region. Future research is required to investigate regions where low-volume centres have specialized PD infrastructure and the potential impact on mortality.

Proposed delay for safe surgery after COVID-19.

BACKGROUND: Long-term effects after COVID-19 may affect surgical safety. This study aimed to evaluate the literature and produce evidence-based guidance regarding the period of delay necessary for adequate recovery of patients following COVID-19 infection before undergoing surgery. METHODS: A rapid review was combined with advice from a working group of 10 clinical experts across Australia and New Zealand. MEDLINE, medRxiv and grey literature were searched to 4 October 2020. The level of evidence was stratified according to the National Health and Medical Research Council evidence hierarchy. RESULTS: A total of 1020 records were identified, from which 20 studies (12 peer-reviewed) were included. None were randomized trials. The studies comprised one case-control study (level III-2 evidence), one prospective cohort study (level III-2) and 18 case-series studies (level IV). Follow-up periods containing observable clinical characteristics ranged from 3 to 16 weeks. New or excessive fatigue and breathlessness were the most frequently reported symptoms. SARS-CoV-2 may impact the immune system for multiple months after laboratory confirmation of infection. For patients with past COVID-19 undergoing elective curative surgery for cancer, risks of pulmonary complications and mortality may be lowest at 4 weeks or later after a positive swab. CONCLUSION: After laboratory confirmation of SARS-CoV-2 infection, minor surgery should be delayed for at least 4 weeks and major surgery for 8-12 weeks, if patient outcome is not compromised. Comprehensive preoperative and ongoing assessment must be carried out to ensure optimal clinical decision-making.

Screening and testing for COVID-19 before surgery.

BACKGROUND: Preoperative screening for coronavirus disease 2019 (COVID-19) aims to preserve surgical safety for both patients and surgical teams. This rapid review provides an evaluation of current evidence with input from clinical experts to produce guidance for screening for active COVID-19 in a low prevalence setting. METHODS: An initial search of PubMed (until 6 May 2020) was combined with targeted searches of both PubMed and Google Scholar until 1 July 2020. Findings were streamlined for clinical relevance through the advice of an expert working group that included seven senior surgeons and a senior medical virologist. RESULTS: Patient history should be examined for potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hyposmia and hypogeusia may present as early symptoms of COVID-19, and can potentially discriminate from other influenza-like illnesses. Reverse transcription-polymerase chain reaction is the gold standard diagnostic test to confirm SARS-CoV-2 infection, and although sensitivity can be improved with repeated testing, the decision to retest should incorporate clinical history and the local supply of diagnostic resources. At present, routine serological testing has little utility for diagnosing acute infection. To appropriately conduct preoperative testing, the temporal dynamics of SARS-CoV-2 must be considered. Relative to other thoracic imaging modalities, computed tomography has the greatest utility for characterizing pulmonary involvement in COVID-19 patients who have been diagnosed by reverse transcription-polymerase chain reaction. CONCLUSION: Through a rapid review of the literature and advice from a clinical expert working group, evidence-based recommendations have been produced for the preoperative screening of surgical patients with suspected COVID-19.

Personal protective equipment and evidence-based advice for surgical departments during COVID-19.

BACKGROUND: Inconsistencies regarding the use of appropriate personal protective equipment (PPE) have raised concerns for the safety of surgical staff during the coronavirus disease 2019 (COVID-19) pandemic. This rapid review synthesizes the literature and includes input from clinical experts to provide evidence-based guidance for surgical services. METHODS: The rapid review comprised of targeted searches in PubMed and grey literature. Pertinent findings were discussed by a working group of clinical experts, and consensus recommendations, consistent with Australian and New Zealand Government guidelines, were formulated. RESULTS: There was a paucity of high-quality primary studies specifically investigating appropriate surgical PPE for healthcare workers treating patients possibly infected with COVID-19. SARS-CoV-2 is capable of aerosol, droplet and fomite transmission, making it essential to augment standard infection control measures with appropriate PPE, especially during surgical emergencies and aerosol-generating procedures. All biological material should be treated a potential source of SARS-COV-2. Staff must have formal training in the use of PPE and should be supervised by a colleague during donning and doffing. Patients with suspected or confirmed COVID-19 should wear a surgical mask during transfer to and from theatre. Potential solutions exist in the literature to extend the use of surgical P2/N95 respirators in situations of limited supply. CONCLUSION: PPE is advised for all high-risk procedures and when a patient's COVID-19 status is unknown. Surgical departments should facilitate staggered rostering, remote meeting attendance, and self-isolation of symptomatic staff. Vulnerable surgical staff should be identified and excluded from operations with a high risk of COVID-19 infection.

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 Royal Australasian College of Surgeons 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 judgement and to enable individualized, 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.

Safe surgery during the coronavirus disease 2019 crisis.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a global pandemic. Surgical care has been impacted, with concerns raised around surgical safety, especially in terms of laparoscopic versus open surgery. Due to potential aerosol transmission of SARS-CoV-2, precautions during aerosol-generating procedures and production of surgical plume are paramount for the safety of surgical teams. METHODS: A rapid review methodology was used with evidence sourced from PubMed, Departments of Health, surgical colleges and other health authorities. From this, a working group of expert surgeons developed recommendations for surgical safety in the current environment. RESULTS: Pre-operative testing of surgical patients with reverse transcription-polymerase chain reaction does not guarantee lack of infectivity due to a demonstrated false-negative rate of up to 30%. All bodily tissues and fluids should therefore be treated as a potential source of COVID-19 infection during operative management. Caution must be taken, especially when using an energy source that produces surgical plumes, and an appropriate capture device should also be used. Limiting the use of such devices or using lower energy devices is desirable. To reduce perceived risks association with desufflation of pneumoperitoneum during laparoscopic surgery, an appropriate suction irrigator system, attached to a high-efficiency particulate air filter, should be used. Additionally, appropriate use of personal protective equipment by the surgical team is necessary during high-risk aerosol-generating procedures. CONCLUSIONS: As a result of the rapid review, evidence-based guidance has been produced to support safe surgical practice.

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.

Oestrogen hormone receptors in focal nodular hyperplasia.

BACKGROUND: The role of hormones in focal nodular hyperplasia (FNH) has been investigated with conflicting results. OBJECTIVE: The aim of this study was to evaluate oestrogen and progesterone receptor immunohistochemical expression in FNH and surrounding normal liver (control material). METHODS: Biopsy materials from FNH and control tissue were investigated using an immunostainer. Receptor expression was graded as the proportion score (percentage of nuclear staining) and oestrogen receptor intensity score. RESULTS: Study material included tissue from 11 resected FNH lesions and two core biopsies in 13 patients (two male). Twelve samples showed oestrogen receptor expression. The percentage of nuclear oestrogen receptor staining was <33% in eight FNH biopsies, 34-66% in two FNH biopsies, and >67% in both core biopsies. The better staining in core biopsies relates to limitations of the staining technique imposed by the fibrous nature of larger resected FNH. Control samples from surrounding tissue were available for nine of the resected specimens and all showed oestrogen receptor expression. Progesterone receptor expression was negligible in FNH and control samples. CONCLUSIONS: By contrast with previous studies, the majority of FNH and surrounding liver in this cohort demonstrated oestrogen receptor nuclear staining. The implications of this for continued oral contraceptive use in women of reproductive age with FNH remain uncertain given the lack of consistent reported growth response to oestrogen stimulation or withdrawal.

Cirrhosis and microvascular invasion predict outcomes in hepatocellular carcinoma.

BACKGROUND: Liver resection (LR) and liver transplantation (LT) are two modalities offering potential for cure in patients with hepatocellular carcinoma (HCC). The objective of this study was to evaluate the long-term survival of patients with HCC treated with LT and LR and to analyse variables influencing these outcomes. METHODS: Patients referred to the South Australian Liver Transplant Unit and Hepatopancreatobiliary Unit at Flinders Medical Centre from January 1992 to September 2009 with a diagnosis of HCC who underwent LT or LR were included in the study. Histopathological parameters analysed included size, number and grade of tumour, microscopic vascular invasion and presence or absence of cirrhosis in remnant liver. RESULTS: Eighty-five patients with a median age of 58 years (range 26-85 years) underwent LT or LR. Median follow-up was 40 months in both groups. Overall, 5-year actuarial survival for all patients with HCC in both groups was 55%. LR patients were significantly older (P < 0.001) than LT patients. Their tumours were larger (P < 001) and more often solitary (P < 0.001) compared with the LT group. In multivariate analysis, age >60 (P < 0.02), histopathological evidence of vascular invasion (P < 0.02) and presence of cirrhosis (P < 0.02) were associated with a significantly reduced survival. Patients without vascular invasion and cirrhosis had an actuarial 5-year survival >70%. CONCLUSIONS: Our study indicates that LT (within University of California, San Francisco criteria) and LR can lead to acceptable long-term survival outcomes in patients with HCC. Microscopic vascular invasion and cirrhosis were the most significant prognostic factors impacting on survival.

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.

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.

Predicting patient survival after pancreaticoduodenectomy for malignancy: histopathological criteria based on perineural infiltration and lymphovascular invasion.

BACKGROUND: Accurate and simple prognostic criteria based on histopathology following pancreaticoduodenectomy would be helpful in assessing prognosis and considering and evaluating adjuvant therapy. This study analysed the histological parameters influencing outcome following pancreaticoduodenectomy for periampullary malignancy. METHODS: A total of 110 pancreaticoduodenectomies were performed from 1998 to 2008. The median age of patients was 69 years (range 20-89 years). The median follow-up was 4.9 years. Of the procedures, 87% (96) were performed for malignancies and the remainder (n= 14) for benign aetiologies. Of the 96 malignancies, 60 were pancreatic adenocarcinoma and the rest were ampullary (14), cholangio (9), duodenal (9) carcinomas and others. Statistical analysis was performed using log-rank and Cox regression multivariate analyses. RESULTS: Patients who underwent resection had 1-, 3- and 5-year survival rates of 70%, 46% and 41%, respectively. The 1-, 3- and 5-year survival rates for periampullary cancers other than pancreatic adenocarcinoma were 83%, 69% and 61%, respectively; those for pancreatic adenocarcinoma were 62%, 31% and 27%, respectively (P < 0.003). Poor tumour differentiation (P < 0.02), tumour size >3 cm (P < 0.04), margin

Influence of resection margin on survival in hepatic resections for colorectal liver metastases.

BACKGROUND: Traditionally a 1-cm margin has been accepted as the gold standard for resection of colorectal liver metastases. Evidence is emerging that a lesser margin may provide equally acceptable outcomes, but a critical margin, below which recurrence is higher and survival poorer, has not been universally agreed. In a recent publication, we reported peri-operative morbidity and clear margin as the two independent prognostic factors. The aim of the current study was to further analyse the effect of the width of the surgical margin on patient survival to determine whether a margin of 1 mm is adequate. METHODS: Two hundred and sixty-one consecutive primary liver resections for colorectal metastases were analysed from 1992 to 2007. The resection margins were assessed by microscopic examination of paraffin sections. The initial analysis was performed on five groups according to the resection margins: involved margin, 0-1 mm, >1-<4 mm, 4-<10 mm and > or = 10 mm. Subsequent analysis was based on two groups: margin <1 mm and >1 mm. RESULTS: With a median follow-up of 4.7 years, the overall 5-year patient and disease-free survival were 38% and 22%, respectively. There was no significant difference in patient- or disease-free survival between the three groups with resection margins >1 mm. When a comparison was made between patients with resection margins < or = 1 mm and patients with resection margins >1 mm, there was a significant 5-year patient survival difference of 25% versus 43% (P < 0.04). However, the disease-free survival difference did not reach statistical significance (P = 0.14). CONCLUSIONS: In this cohort of patients, we have demonstrated that a resection margin of greater than 1 mm is associated with significantly improved 5-year overall survival, compared with involved margins or margins less than or equal to 1 mm. The possible beneficial effect of greater margins beyond 1 mm could not be demonstrated.

Donor mannose-binding lectin deficiency increases the likelihood of clinically significant infection after liver transplantation.

BACKGROUND: Mannose-binding lectin (MBL) is an important mediator of innate immunity and is synthesized primarily by the liver. Low MBL levels are common, are due primarily to polymorphisms in the gene encoding MBL (MBL2), and are associated with an increased risk of infection, particularly when immunity is compromised. We report a large, retrospective study that examined the association between MBL status and clinically significant infection following orthotopic liver transplantation. METHODS: One hundred two donor-recipient orthotopic liver transplantation pairs were studied. Five polymorphisms in the promoter and coding regions of MBL2 were examined. MBL levels were measured, using the mannan-binding and C4-deposition assays, in serum samples obtained before and after transplantation. Associations between MBL status, as assessed by serum MBL levels and MBL2 genotype, and time to first clinically significant infection (CSI) after transplantation were examined in survival analysis with consideration of competing risks. RESULTS: The median duration of follow-up after orthotopic liver transplantation was 4 years. Thirty-six percent of recipients developed CSI after transplantation. The presence of MBL2 coding mutations in the donor was significantly associated with CSI in the recipient; the cumulative incidence function of infection was 55% in recipients of deficient livers, compared with 32% for recipients of wild-type livers (P = .002). Infection was not associated with recipient MBL2 genotype. Low MBL levels after orthotopic liver transplantation levels (mannan-binding <1 microg/mL or C4 deposition <0.2 C4 U/microL) were also associated with CSI (cumulative incidence function, 52% vs. 20%, P = .003; and cumulative incidence function, 54% vs. 24%, P = .007, respectively). In multivariate analysis, mutation in the MBL2 coding region of the donor (hazard ratio, 2.8; P = .005) and the use of cytomegalovirus prophylaxis (hazard ratio, 2.6; P = .005) were independently associated with CSI. CONCLUSIONS: Recipients of MBL-deficient livers have almost a 3-fold greater likelihood of developing CSI and may benefit from MBL replacement.

Intermittent ischemia but not ischemic preconditioning is effective in restoring bile flow after ischemia reperfusion injury in the livers of aged rats.

BACKGROUND/AIMS: 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 INT 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.

Liver transplantation: a small-volume unit experience.

BACKGROUND: Results of liver transplantation have improved significantly over the last three decades. Hospital volume has been cited as an important outcome factor. The South Australian (SA) programme commenced in 1992 as the fourth centre in Australia. METHODS: Patient and graft survival curves were computed from the Australian and New Zealand (ANZ) Liver Transplant Registry. SA results were compared with the rest of ANZ. All recipients of a cadaveric liver from the start of the SA programme in 1992 until the 100th case in 2005 were included and compared with recipients from ANZ in the same period. RESULTS: In SA, 100 recipients received 104 grafts (average 8.0/year). In the same period 1438 recipients received 1530 grafts in ANZ (mean 23.4/year per unit). The median follow up was 6.2 years. Patient and graft survival curves were similar (P = 0.51, log-rank test.) Survival rates at 1, 5 and 10 years were 0.93, 0.83, 0.61 and 0.88, 0.80, 0.72 for SA and ANZ, respectively (P = NS). There was trend towards a higher mortality rate of recurrent hepatitis C in SA patients when compared with the rest of ANZ (4.0 vs 1.3% respectively, P = 0.06). Recipient variables, such as age and primary liver disease did not differ between SA and ANZ. For the SA patients the biliary anastomotic stricture rate was 20%, primary non-function rate was 2%, hepatic artery thrombosis 1% and portal vein thrombosis 1%. CONCLUSION: Good results are possible in a small-volume unit for cadaveric adult liver transplant.

Ischemic preconditioning and intermittent ischemia preserve bile flow in a rat model of ischemia/reperfusion injury.

Ischemia and reperfusion (IR) injury of the liver is associated with impaired bile secretion, but the effects of ischemic preconditioning (IPC) and intermittent ischemia (INT) on bile flow are unknown. A rat model of segmental (60%-70%) hepatic ischemia and reperfusion was employed to test the effects of IPC and INT on bile flow. Continuous clamping for 45 min (CC) substantially reduced bile flow, and this did not recover after 60 min of reperfusion. IPC and INT caused a significant recovery of bile flow. The elevation in plasma liver marker enzymes induced by CC was not reduced by IPC and INT. Light microscopy showed mild hepatocyte damage in all groups. In the CC group, the amount of F-actin localized around the bile canaliculi in the ischemic lobes was less than that in the nonischemic lobes, but this difference was not observed in the IPC and INT groups. It is concluded that IPC and INT substantially alleviate the decrease in bile flow induced by ischemia. Bile flow may be useful in the assessment of IR injury.

Ischemic preconditioning and intermittent ischemia preserve bile flow in a rat model of ischemia reperfusion injury.

Ischemia and reperfusion (IR) injury of the liver is associated with impaired bile secretion, but the effects of ischemic preconditioning (IPC) and intermittent ischemia (INT) on bile flow are unknown. A rat model of segmental (60%-70%) hepatic ischemia and reperfusion was employed to test the effects of IPC and INT on bile flow. Continuous clamping for 45 min (CC) substantially reduced bile flow, and this did not recover after 60 min of reperfusion. IPC and INT caused a significant recovery of bile flow. The elevation in plasma liver marker enzymes induced by CC was not reduced by IPC and INT. Light microscopy showed mild hepatocyte damage in all groups. In the CC group, the amount of F-actin localized around the bile canaliculi in the ischemic lobes was less than that in the nonischemic lobes, but this difference was not observed in the IPC and INT groups. It is concluded that IPC and INT substantially alleviate the decrease in bile flow induced by ischemia. Bile flow may be useful in the assessment of IR injury.