Publications by authors named "Stuart McCluskey"

114 Publications

Adult liver transplant anesthesiology practice patterns and resource utilization in the United States: Survey results from the society for the advancement of transplant anesthesia.

Clin Transplant 2021 Oct 12:e14504. Epub 2021 Oct 12.

Department of Anesthesiology, University of Colorado, Aurora, CO.

Introduction: Liver transplant anesthesiology is an evolving and expanding subspecialty, and programs have, in the past, exhibited significant variations of practice at transplant centers across the United States. In order to explore current practice patterns, the Quality & Standards Committee from the Society for the Advancement of Transplant Anesthesia (SATA) undertook a survey of liver transplant anesthesiology program directors.

Methods: Program directors were invited to participate in an online questionnaire. A total of 110 program directors were identified from the 2018 Scientific Registry of Transplant Recipients (SRTR) database. Replies were received from 65 programs (response rate of 59%).

Results: Our results indicate an increase in transplant anesthesia fellowship training and advanced training in transesophageal echocardiography (TEE). We also find that the use of intraoperative TEE and viscoelastic testing is more common. However, there has been a reduction in the use of veno-venous bypass, routine placement of pulmonary artery catheters and the intraoperative use of anti-fibrinolytics when compared to prior surveys.

Conclusion: The results show considerable heterogeneity in practice patterns across the country that continues to evolve. However, there appears to be a movement towards the adoption of specific structural and clinical practices. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/ctr.14504DOI Listing
October 2021

Normal Saline for Kidney Transplantation Surgery: Less Is More.

Anesthesiology 2021 10;135(4):564-567

the Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Canada; the Department of Anesthesia and Pain Management, and Multiorgan Transplant Program, University Health Network, Toronto, Canada.

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http://dx.doi.org/10.1097/ALN.0000000000003948DOI Listing
October 2021

The effect of perioperative packed red blood cells transfusion on patient outcomes after liver transplant for hepatocellular carcinoma.

HPB (Oxford) 2021 Jul 5. Epub 2021 Jul 5.

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Department of Surgery, University Health Network-Toronto General Hospital, Toronto, Ontario, Canada; Multi-Organ Transplant, University Health Network-Toronto General Hospital, Toronto, Ontario, Canada. Electronic address:

Background: The impact of packed Red Blood Cell (pRBC) transfusion on oncological outcomes after liver transplantation (LT) for Hepatocellular Carcinoma (HCC) remains controversial. We evaluated the impact of pRBC transfusion on HCC recurrence and overall survival (OS) after LT for HCC.

Methods: Patients with HCC transplanted between 2000 and 2018 were included and stratified by receipt of pRBC transfusion. Outcomes were HCC recurrence and OS. Propensity score matching was performed to account for confounders.

Results: Of the 795 patients, 234 (29.4%) did not receive pRBC transfusion. After matching the 1-, 3-, and 5-year cumulative incidence of recurrence was 6.6%, 12.5% and 14.8% for no-pRBC transfusion, and 8.6%, 18.8% and 21.3% (p = 0.61) for pRBC transfusion. The OS at 1-, 3-, 5-year was 93.0%, 84.6% and 75.8% vs 92.0%, 79.7% and 73.5% (p = 0.83) for no-pRBC transfusion and pRBC transfusion, respectively. There were no differences in recurrence (HR 1.13, 95%CI 0.71-1.78, p = 0.61) or OS (HR 1.04, 95%CI 0.71-1.54, p = 0.83).

Conclusion: Perioperative administration of pRBC in liver transplant recipients for HCC resulted in a nonsignificant increase of HCC recurrence and death after accounting for confounder. Surgeons should continue to exercise cation and optimize patients iron stores medically preoperatively.
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http://dx.doi.org/10.1016/j.hpb.2021.06.425DOI Listing
July 2021

Albumin use in bleeding cardiac surgical patients and associated patient outcomes.

Can J Anaesth 2021 10 26;68(10):1514-1526. Epub 2021 Jul 26.

Department of Anesthesia and Pain Management, Toronto General Hospital - University Health Network, Sinai Health System, Women's College Hospital, University of Toronto, 200 Elizabeth Street, 3EN-464, Toronto, ON, M5G 2C4, Canada.

Purpose: Albumin solution is a colloid used for resuscitation in cardiac surgical patients, but it is unclear if it offers advantages over crystalloids. We examined current clinical practice across 11 cardiac surgical centres and the association of albumin with outcomes in a cohort of bleeding cardiac surgical patients.

Methods: This was a post hoc analysis of data from the Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery (FIBRES) trial. Multivariable regression models adjusted for demographic and surgical characteristics were used to examine predictors of early albumin administration (within the initial 24 perioperative hours), late albumin administration (from 24 hr to seven days after cardiopulmonary bypass), and the association of albumin use with 28-day acute kidney injury, mortality, and length of hospital and intensive care unit (ICU) stay.

Results: Of the 735 patients included, 525 (71%) received albumin, ranging from 4.8% to 97.4% of patients across institutions, with 475 (64.6%) receiving albumin early (5% or 25% solution). In the adjusted models, female sex and preoperative hospital admission were associated with early use, while heart failure, female sex, bleeding severity, older age, and prior albumin use were predictors of later administration. Early albumin use was not associated with differences in acute kidney injury (adjusted odds ratio [aOR] 1.77; 95% confidence interval [CI], 0.96 to 3.27; P = 0.07), mortality (aOR 1.66; 95% CI, 0.99 to 2.78; P = 0.05), or length of ICU stay (P = 0.11) or hospital stay (P = 0.67).

Conclusions: Albumin use is common but highly variable within and across sites. Albumin use was not associated with improved outcomes. High quality randomized controlled trials should clarify its role in cardiac surgical patients.
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http://dx.doi.org/10.1007/s12630-021-02070-7DOI Listing
October 2021

Anesthesia for the Patient with Severe Liver Failure.

Adv Anesth 2020 12;38:251-267

Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, 3 Eaton North, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada. Electronic address:

The incidence of liver failure continues to increase, and it is associated with increased perioperative morbidity and mortality. Liver failure is associated with multiorgan dysfunction, including central nervous, cardiac, respiratory, gastrointestinal, renal, and hematological systems. Preoperative identification, optimization, and tailored anesthetic management are essential for optimum outcomes in patients with liver disease undergoing surgery. The coagulopathy of liver failure is a balanced coagulopathy better assessed by thromboelastography than conventional testing, and it is not directly associated with bleeding risk.
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http://dx.doi.org/10.1016/j.aan.2020.09.002DOI Listing
December 2020

Enhanced Recovery for Liver Transplantation: A First Step on a Long Road.

Transplantation 2021 May 6. Epub 2021 May 6.

Department of Anesthesiology and Pain Medicine, University of Toronto, Canada Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Department of Surgery, University of Toronto, Canada Multi-Organ Transplant, Department of Medicine, University of Toronto, Canada Multi-Organ Transplant, Anesthesiology and Pain Medicine, University of Toronto, Canada.

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http://dx.doi.org/10.1097/TP.0000000000003809DOI Listing
May 2021

Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery: A Randomized Pilot Trial.

JAMA Netw Open 2021 04 1;4(4):e213936. Epub 2021 Apr 1.

Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Importance: Approximately 15% of patients undergoing cardiac surgery receive frozen plasma (FP) for bleeding. Four-factor prothrombin complex concentrates (PCCs) have logistical and safety advantages over FP and may be a suitable alternative.

Objectives: To determine the proportion of patients who received PCC and then required FP, explore hemostatic effects and safety, and assess the feasibility of study procedures.

Design, Setting, And Participants: Parallel-group randomized pilot study conducted at 2 Canadian hospitals. Adult patients requiring coagulation factor replacement for bleeding during cardiac surgery (from September 23, 2019, to June 19, 2020; final 28-day follow-up visit, July 17, 2020). Data analysis was initiated on September 15, 2020.

Interventions: Prothrombin complex concentrate (1500 IU for patients weighing ≤60 kg and 2000 IU for patients weighing >60 kg) or FP (3 U for patients weighing ≤60 kg and 4 U for patients weighing >60 kg), repeated once as needed within 24 hours (FP used for any subsequent doses in both groups). Patients and outcome assessors were blinded to treatment allocation.

Main Outcomes And Measures: Hemostatic effectiveness (whether patients received any hemostatic therapies from 60 minutes to 4 and 24 hours after initiation of the intervention, amount of allogeneic blood components administered within 24 hours after start of surgery, and avoidance of red cell transfusions within 24 hours after start of surgery), protocol adherence, and adverse events. The analysis set comprised all randomized patients who had undergone cardiac surgery, received at least 1 dose of either treatment, and provided informed consent after surgery.

Results: Of 169 screened patients, 131 were randomized, and 101 were treated (54 with PCC and 47 with FP), provided consent, and were included in the analysis (median age, 64 years; interquartile range [IQR], 54-73 years; 28 [28%] were female; 82 [81%] underwent complex operations). The PCC group received a median 24.9 IU/kg (IQR, 21.8-27.0 IU/kg) of PCC (2 patients [3.7%; 95% CI, 0.4%-12.7%] required FP). The FP group received a median 12.5 mL/kg (IQR, 10.0-15.0 mL/kg) of FP (4 patients [8.5%; 95% CI, 2.4%-20.4%] required >2 doses of FP). Hemostatic therapy was not required at the 4-hour time point for 43 patients (80%) in the PCC group and for 32 patients (68%) in the FP group (P = .25) nor at the 24-hour time point for 41 patients (76%) in the PCC group and for 31 patients (66%) patients in the FP group (P = .28). The median numbers of units for 24-hour cumulative allogeneic transfusions (red blood cells, platelets, and FP) were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 14.0 U (IQR, 8.0-20.0 U) in the FP group (ratio, 0.58; 95% CI, 0.45-0.77; P < .001). After exclusion of FP administered as part of the investigational medicinal product, the median numbers of units were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 10.0 U (IQR, 6.0-16.0 U) in the FP group (ratio, 0.80; 95% CI, 0.59-1.08; P = .15). For red blood cells alone, the median numbers were 1.5 U (IQR, 0.0-4.0 U) in the PCC group and 3.0 U (IQR, 1.0-5.0 U) in the FP group (ratio, 0.69; 95% CI, 0.47-0.99; P = .05). During the first 24 hours after start of surgery, 15 patients in the PCC group (28%) and 8 patients in the FP group (17%) received no red blood cells (P = .24). Adverse event profiles were similar.

Conclusions And Relevance: This randomized clinical trial found that the study protocols were feasible. Adequately powered randomized clinical trials are warranted to determine whether PCC is a suitable substitute for FP for mitigation of bleeding in cardiac surgery.

Trial Registration: ClinicalTrials.gov Identifier: NCT04114643.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017469PMC
April 2021

Blood Cell Salvage and Autotransfusion Does Not Worsen Oncologic Outcomes Following Liver Transplantation with Incidental Hepatocellular Carcinoma: A Propensity Score-Matched Analysis.

Ann Surg Oncol 2021 Oct 28;28(11):6816-6825. Epub 2021 Mar 28.

HBP and Multi Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada.

Background: Intraoperative blood cell salvage and autotransfusion (IBSA) during liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial for concern regarding adversely impacting oncologic outcomes.

Objective: We aimed to evaluate the long-term oncologic outcomes of patients who underwent LT with incidentally discovered HCC who received IBSA compared with those who did not receive IBSA.

Methods: Patients undergoing LT (January 2001-October 2018) with incidental HCC on explant pathology were retrospectively identified. A 1:1 propensity score matching (PSM) was performed. HCC recurrence and patient survival were compared. Kaplan-Meier survival analyses were performed, and univariable Cox proportional hazard analyses were performed for risks of recurrence and death.

Results: Overall, 110 patients were identified (IBSA, n = 76 [69.1%]; non-IBSA, n = 34 [30.9%]). Before matching, the groups were similar in terms of demographics, transplant, and tumor characteristics. Overall survival was similar for IBSA and non-IBSA at 1, 3, and 5 years (96.0%, 88.4%, 83.0% vs. 97.1%, 91.1%, 87.8%, respectively; p = 0.79). Similarly, the recurrence rate at 1, 3, and 5 years was not statistically different (IBSA 0%, 1.8%, 1.8% vs. non-IBSA 0%, 3.2%, 3.2%, respectively; p = 0.55). After 1:1 matching (26 IBSA, 26 non-IBSA), Cox proportional hazard analysis demonstrated similar risk of death and recurrence between the groups (IBSA hazard ratio [HR] of death 1.26, 95% confidence interval [CI] 0.52-3.05, p = 0.61; and HR of recurrence 2.64, 95% CI 0.28-25.30, p = 0.40).

Conclusions: IBSA does not appear to adversely impact oncologic outcomes in patients undergoing LT with incidental HCC. This evidence further supports the need for randomized trials evaluating the impact of IBSA use in LT for HCC.
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http://dx.doi.org/10.1245/s10434-021-09863-6DOI Listing
October 2021

A Pragmatic Non-Randomized Trial of Prehabilitation Prior to Cancer Surgery: Study Protocol and COVID-19-Related Adaptations.

Front Oncol 2021 10;11:629207. Epub 2021 Mar 10.

Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Background: Experimental data highlight the potential benefits and health system cost savings related to surgical prehabilitation; however, adequately powered randomized controlled trial (RCT) data remain nascent. Emerging prehabilitation services may be informed by early RCT data but can be limited in informing real-world program development. Pragmatic trials emphasize external validity and generalizability to understand and advise intervention development and implementation in clinical settings. This paper presents the methodology of a pragmatic prehabilitation trial to complement emerging phase III clinical trials and inform implementation strategies.

Methods: This is a pilot pragmatic clinical trial conducted in a large academic hospital in Toronto, Ontario, Canada to assess feasibility of clinical implementation and derive estimates of effectiveness. Feasibility data include program referral rates, enrolment and attrition, intervention adherence and safety, participant satisfaction, and barriers and facilitators to programming. The study aims to receive 150 eligible referrals for adult, English-speaking, preoperative oncology patients with an identified indication for prehabilitation (., frailty, deconditioning, malnutrition, psychological distress). Study participants undergo a baseline assessment and shared-decision making regarding the intervention setting: either facility-based prehabilitation or home-based prehabilitation. In both scenarios, participants receive an individualized exercise prescription, stress-reduction psychological support, nutrition counseling, and protein supplementation, and if appropriate, smoking cessation program referrals. Secondary objectives include estimating intervention effects at the week prior to surgery and 30 and 90 days postoperatively. Outcomes include surgical complications, postoperative length of stay, mortality, hospital readmissions, physical fitness, psychological well-being, and quality of life. Data from participants who decline the intervention but consent for research-related access to health records will serve as comparators. The COVID-19 pandemic required the introduction of a 'virtual program' using only telephone or internet-based communication for screening, assessments, or intervention was introduced.

Conclusion: This pragmatic trial will provide evidence on the feasibility and viability of prehabilitation services delivered under usual clinical conditions. Study amendments due to the COVID-19 pandemic are presented as strategies to maintain prehabilitation research and services to potentially mitigate the consequences of extended surgery wait times.
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http://dx.doi.org/10.3389/fonc.2021.629207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987917PMC
March 2021

MRI-guided Focused Ultrasound Ablation for Localized Intermediate-Risk Prostate Cancer: Early Results of a Phase II Trial.

Radiology 2021 03 2;298(3):695-703. Epub 2021 Feb 2.

From the Joint Department of Medical Imaging (S.G., R.C., E.H., M.A.H., W.K.), Division of Urology, Department of Surgical Oncology (A.F., K.C., S.J., A.K., A.R.Z., R.J.H., N.P.), Biostatistics Department, Princess Margaret Cancer Centre (X.L.), Department of Anaesthesia (S.M.), and Department of Pathology, Laboratory Medicine Program (T.H.v.d.K.), University Health Network-Mount Sinai Hospital-Women's, College Hospital, University of Toronto, 585 University Ave, Toronto, ON, Canada M5G 2N2; and Department of Urology, Oakville Trafalgar Memorial Hospital, Toronto, Canada (P.F.I.).

Background To reduce adverse effects of whole-gland therapy, participants with localized clinically significant prostate cancer can undergo MRI-guided focal therapy. Purpose To explore safety and early oncologic and functional outcomes of targeted focal high-intensity focused ultrasound performed under MRI-guided focused ultrasound for intermediate-risk clinically significant prostate cancer. Materials and Methods In this prospective phase II trial, between February 2016 and July 2019, men with unifocal clinically significant prostate cancer visible at MRI were treated with transrectal MRI-guided focused ultrasound. The primary end point was the 5-month biopsy (last recorded in December 2019) with continuation to the 24-month follow-up projected to December 2021. Real-time ablation monitoring was performed with MR thermography. Nonperfused volume was measured at treatment completion. Periprocedural complications were recorded. Follow-up included International Prostate Symptom Score (IPSS) and International Index of Erectile Function-15 (IIEF-15) score at 6 weeks and 5 months, and multiparametric MRI and targeted biopsy of the treated area at 5 months. The generalized estimating equation model was used for statistical analysis, and the Holm method was used to adjust value. Results Treatment was successfully completed in all 44 men, 36 with grade group (GG) 2 and eight with GG 3 disease (median age, 67 years; interquartile range [IQR], 62-70 years). No major treatment-related adverse events occurred. Forty-one of 44 participants (93%; 95% CI: 82, 98) were free of clinically significant prostate cancer (≥6 mm GG 1 disease or any volume ≥GG 2 disease) at the treatment site at 5-month biopsy (median, seven cores). Median IIEF-15 and IPSS scores were similar at baseline and at 5 months (IIEF-15 score at baseline, 61 [IQR, 34-67] and at 5 months, 53 [IQR, 24-65.5], = .18; IPSS score at baseline, 3.5 [IQR, 1.8-7] and at 5 months, 6 [IQR, 2-7.3], = .43). Larger ablations (≥15 cm) compared with smaller ones were associated with a decline in IIEF-15 scores at 6 weeks (adjusted < .01) and at 5 months (adjusted = .07). Conclusion Targeted focal therapy of intermediate-risk prostate cancer performed with MRI-guided focused ultrasound ablation was safe and had encouraging early oncologic and functional outcomes. © RSNA, 2021 See also the editorial by Tempany-Afdhal in this issue.
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http://dx.doi.org/10.1148/radiol.2021202717DOI Listing
March 2021

Predicting Early Extubation After Liver Transplantation: External Validation and Improved Generalizability of a Proposed Fast-track Score.

Transplantation 2021 Sep;105(9):2029-2036

Department of Anesthesia and Pain Medicine, University of Toronto, Toronto, ON, Canada.

Background: Early extubation of liver transplantation recipients is a cornerstone of fast-track (FT) pathways. Identifying suitable candidates has previously been accomplished using perioperative variables to develop a FT probability score. The objective of this study was to externally validate a proposed FT score.

Methods: Following Research Ethics Board approval, data were extracted on liver transplants conducted at a single center from 2009 to 2017. Data extracted included patient characteristics, intraoperative variables, and postoperative outcome variables. The proposed FT score utilized 9 variables: age, gender, body mass index, model of end-stage liver disease, retransplant, preoperative hospital admission, blood transfusion, operative time, and vasopressor use. We calculated the FT score in our cohort, and assessed the discrimination and calibration of the model. Score performance was explored by subgroup analyses, customization and altering the outcome definition.

Results: The FT score was found to predict higher rates of successful FT than was observed in the external cohort (n = 1385) and had reduced discrimination (area under the receiver operating curve, 0.711; 95% confidence interval, 0.682-0.741) compared with the original internal validation cohort (area under the receiver operating curve, 0.830; 95% confidence interval, 0.789-0.871; P < 0.0001). Discrimination was improved by customizing the transfusion (P < 0.0001) components of the simplified score or by level 1 customization of all regression model coefficients (P < 0.0001). A time-based definition of FT (early extubation) did not alter the accuracy of the prediction score (P = 0.914), improving the model's generalizability.

Conclusions: The proposed FT score may help identify patients suitable for early extubation and FT pathways after liver transplantation in conjunction with clinical judgment.
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http://dx.doi.org/10.1097/TP.0000000000003452DOI Listing
September 2021

Renal Dysfunction After Liver Transplantation: Effect of Donor Type.

Liver Transpl 2020 06 23;26(6):799-810. Epub 2020 Apr 23.

Multi-Organ Transplant Program, Toronto General Hospital, Toronto, ON, Canada.

Recipients of donation after circulatory death (DCD) grafts are reportedly at higher risk of developing renal dysfunction after liver transplantation (LT). We compared the development of acute kidney injury (AKI) and chronic kidney disease (CKD) after LT in recipients of DCD versus donation after brain death (DBD) or living donor liver transplantation (LDLT) livers. Adult recipients of DBD, LDLT, and DCD between 2012 and 2016 at Toronto General Hospital were included. AKI was defined as a post-LT increase of serum creatinine (sCr) ≥26.5 µmol/L within 48 hours or a ≥50% increase from baseline, and CKD was defined as an estimated glomerular filtration rate <60 mL/minute for >3 months. A total of 681 patients (DCD, n = 57; DBD, n = 446; and LDLT, n = 178) with similar baseline comorbidities were included. Perioperative AKI (within the first 7 postoperative days) was observed more frequently in the DCD group (61%; DBD, 40%; and LDLT, 44%; P = 0.01) and was associated with significantly higher peak AST levels (P < 0.001). Additionally, patients in the DCD group had a significantly higher peak sCr (P < 0.001) and a trend toward higher rates of AKI stage 3 (DCD, 33%; DBD, 21%; LDLT, 21%; P = 0.11). The proportions of recovery from AKI (DCD, 77%; DBD, 72%; LDLT, 78%; P = 0.45) and patients developing CKD (DCD, 33%; DBD, 32%; LDLT, 32%; P = 0.99) were similar. Nevertheless, patients who received DCD or DBD LT and required perioperative renal replacement therapy showed significantly lower patient survival in multivariate analysis (hazard ratio, 7.90; 95% confidence interval, 4.51-13.83; P < 0.001). In conclusion, recipients of DCD liver grafts experience higher rates of short-term post-LT renal dysfunction compared with DBD or LDLT. Additional risk factors for the development of severe kidney injury, such as high Model for End-Stage Liver Disease score, massive transfusions, or donor age ≥60 years should be avoided.
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http://dx.doi.org/10.1002/lt.25755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317208PMC
June 2020

Anesthesia for the Patient with Severe Liver Failure.

Anesthesiol Clin 2020 Mar 3;38(1):35-50. Epub 2020 Jan 3.

Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, 3 Eaton North, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada. Electronic address:

The incidence of liver failure continues to increase, and it is associated with increased perioperative morbidity and mortality. Liver failure is associated with multiorgan dysfunction, including central nervous, cardiac, respiratory, gastrointestinal, renal, and hematological systems. Preoperative identification, optimization, and tailored anesthetic management are essential for optimum outcomes in patients with liver disease undergoing surgery. The coagulopathy of liver failure is a balanced coagulopathy better assessed by thromboelastography than conventional testing, and it is not directly associated with bleeding risk.
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http://dx.doi.org/10.1016/j.anclin.2019.10.002DOI Listing
March 2020

The chloride horse and normal saline cart: the association of crystalloid choice with acid base status and patient outcomes in kidney transplant recipients.

Can J Anaesth 2020 04 30;67(4):403-407. Epub 2020 Jan 30.

Department of Anesthesia, University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1007/s12630-020-01578-8DOI Listing
April 2020

Advances in CNS PET: the state-of-the-art for new imaging targets for pathophysiology and drug development.

Eur J Nucl Med Mol Imaging 2020 02 21;47(2):451-489. Epub 2019 Sep 21.

Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital, London, UK.

Purpose: A limit on developing new treatments for a number of central nervous system (CNS) disorders has been the inadequate understanding of the in vivo pathophysiology underlying neurological and psychiatric disorders and the lack of in vivo tools to determine brain penetrance, target engagement, and relevant molecular activity of novel drugs. Molecular neuroimaging provides the tools to address this. This article aims to provide a state-of-the-art review of new PET tracers for CNS targets, focusing on developments in the last 5 years for targets recently available for in-human imaging.

Methods: We provide an overview of the criteria used to evaluate PET tracers. We then used the National Institute of Mental Health Research Priorities list to identify the key CNS targets. We conducted a PubMed search (search period 1st of January 2013 to 31st of December 2018), which yielded 40 new PET tracers across 16 CNS targets which met our selectivity criteria. For each tracer, we summarised the evidence of its properties and potential for use in studies of CNS pathophysiology and drug evaluation, including its target selectivity and affinity, inter and intra-subject variability, and pharmacokinetic parameters. We also consider its potential limitations and missing characterisation data, but not specific applications in drug development. Where multiple tracers were present for a target, we provide a comparison of their properties.

Results And Conclusions: Our review shows that multiple new tracers have been developed for proteinopathy targets, particularly tau, as well as the purinoceptor P2X7, phosphodiesterase enzyme PDE10A, and synaptic vesicle glycoprotein 2A (SV2A), amongst others. Some of the most promising of these include F-MK-6240 for tau imaging, C-UCB-J for imaging SV2A, C-CURB and C-MK-3168 for characterisation of fatty acid amide hydrolase, F-FIMX for metabotropic glutamate receptor 1, and F-MNI-444 for imaging adenosine 2A. Our review also identifies recurrent issues within the field. Many of the tracers discussed lack in vivo blocking data, reducing confidence in selectivity. Additionally, late-stage identification of substantial off-target sites for multiple tracers highlights incomplete pre-clinical characterisation prior to translation, as well as human disease state studies carried out without confirmation of test-retest reproducibility.
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http://dx.doi.org/10.1007/s00259-019-04488-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974496PMC
February 2020

Imaging of Chemotherapy-Induced Acute Cardiotoxicity with F-Labeled Lipophilic Cations.

J Nucl Med 2019 12 30;60(12):1750-1756. Epub 2019 May 30.

Invicro LLC, London, United Kingdom.

Many chemotherapy agents are toxic to the heart, such that increasing numbers of cancer survivors are now living with the potentially lethal cardiovascular consequences of their treatment. Earlier and more sensitive detection of chemotherapy-induced cardiotoxicity may allow improved treatment strategies and increase long-term survival. Lipophilic cation PET tracers may be suitable for early detection of cardiotoxicity. This study aimed to evaluate an F-labeled lipophilic phosphonium cation, [1-(2-F-fluoroethyl),1[1,2,3]triazole-4-ethylene]triphenylphosphonium bromide (F-MitoPhos), as a cardiac imaging agent, comparing it with leading PET and SPECT lipophilic cationic tracers before further assessing its potential for imaging cardiotoxicity in an acute doxorubicin model. Cardiac uptake and response to decreased mitochondrial membrane potential of F-MitoPhos and Tc-sestamibi were tested in isolated perfused rat hearts. Baseline pharmacokinetic profiles of F-MitoPhos and F-fluorobenzyltriphenylphosphonium and their response to acute doxorubicin-induced cardiotoxicity were assessed in rats in vivo (10, 15, or 20 mg of doxorubicin per kilogram, intravenously, 48 h beforehand). Cardiac retention of F-MitoPhos was more than double that of Tc-sestamibi in isolated perfused rat hearts. A favorable biodistribution of F-MitoPhos in vivo was observed, with heart-to-tissue ratios of 304 ± 186, 11.2 ± 1.2, and 3.8 ± 0.6 for plasma, liver, and lung, respectively (60 min). A significant dose-dependent loss of cardiac retention of F-MitoPhos was observed on doxorubicin treatment, with average cardiac SUV from 30 to 60 min (mean ± SD) decreasing from 3.5 ± 0.5 (control) to 1.8 ± 0.1 (doxorubicin, 20 mg/kg). Other assessed biomarkers showed no alterations. F-MitoPhos showed pharmacokinetic parameters suitable for cardiac imaging. A significant dose response of cardiac uptake to doxorubicin treatment was observed before detectable biomarker alterations. F-MitoPhos is therefore a promising tracer for imaging chemotherapy-induced cardiotoxicity. To our knowledge, this is the first demonstration of radiolabeled lipophilic cations being used for the PET imaging of chemotherapy-induced cardiotoxicity and indicates the potential application of these compounds in this area.
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http://dx.doi.org/10.2967/jnumed.119.226787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894381PMC
December 2019

Restrictive Versus Liberal Fluid Regimens in Patients Undergoing Pancreaticoduodenectomy: a Systematic Review and Meta-Analysis.

J Gastrointest Surg 2019 06 22;23(6):1250-1265. Epub 2019 Jan 22.

Department of Anaesthesia and Pain Medicine, Middlemore Hospital, 100 Hospital Road, Otahuhu, Auckland, 2025, New Zealand.

Background: Pancreaticoduodenectomy is associated with significant morbidity and mortality which may be influenced by perioperative fluid management. It remains unclear whether liberal and restrictive fluid regimens impact mortality and morbidity in patients undergoing pancreaticoduodenectomy.

Methods: Medline, EMBASE, Cochrane Library and clinicaltrials.gov were searched for studies comparing restrictive and liberal perioperative fluids in patients undergoing pancreaticoduodenectomy. Both prospective and retrospective studies in those undergoing pancreaticoduodenectomy were eligible for inclusion where the patient outcomes were stratified to restrictive and liberal perioperative fluid management regimens, with mortality as the primary outcome. Following study identification, a systematic review and meta-analysis with trial sequential analysis was completed.

Results: Thirteen studies including five prospective trials and eight retrospective analyses totalling 3062 patients were included. Restrictive fluid regimens were associated with a significant reduction in mortality compared to liberal fluid regimens for the overall cohort (odds ratio 0.54; 95% CI 0.31-0.94, p = 0.03). There were no significant differences in complication profile. Subgroup analysis revealed this result was contributed to significantly by retrospective studies. The results of the trial sequential analysis suggest this mortality benefit may be due to a type I statistical error and that further patient numbers are required for definitive conclusions.

Conclusions: Restrictive fluid regimens are associated with a reduction in mortality following pancreaticoduodenectomy. The clinical relevance of this finding needs to be interpreted pragmatically given the lack of association with significant causes of morbidity and in considering the results of the recently published RELIEF study.
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http://dx.doi.org/10.1007/s11605-018-04089-6DOI Listing
June 2019

Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.

BMJ Open 2019 01 15;9(1):e023455. Epub 2019 Jan 15.

Queen Mary University of London, London, UK.

Introduction: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice.

Methods: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide.

Ethics/dissemination: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal.

Trial Registration Number: ISRCTN39653756.
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http://dx.doi.org/10.1136/bmjopen-2018-023455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341180PMC
January 2019

Patient blood management for liver resection: consensus statements using Delphi methodology.

HPB (Oxford) 2019 04 13;21(4):393-404. Epub 2018 Nov 13.

Department of Surgery, Odette Cancer Centre - Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada.

Background: Blood loss and transfusion remain a significant concern in liver resection (LR). Patient blood management (PBM) programs reduce use of transfusions and improve outcomes and costs, but are not standardized for LR. This study sought to create an expert consensus statement on PBM for LR using modified Delphi methodology.

Methods: An expert panel representing hepato-biliary surgery, anesthesiology, and transfusion medicine was invited to participate. 28 statements addressing the 3 pillars of PBM were created. Panelists were asked to rate statements on a 7-point Likert scale. Three-rounds of iterative rating and feedback were completed anonymously, followed by an in-person meeting. Consensus was reached with at least 70% agreement.

Results: The 35 experts panel recommended routine pre-operative transfusion risk assessment, and investigation and management of anemia with iron supplementation. Intra-operatively, restrictive fluid administration without routine central line insertion was recommended, along with intermittent hepatic pedicle occlusion and surgical techniques considerations. Specific criteria for restrictive intra-operative and post-operative transfusion strategy were recommended.

Conclusions: PBM for LR included medical and technical interventions throughout the perioperative continuum, addressing specificities of LR. Diffusion and adoption of these recommendations can standardize PBM for LR to improve patient outcomes and resource utilization.
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http://dx.doi.org/10.1016/j.hpb.2018.09.022DOI Listing
April 2019

In-hospital opioid consumption, but not pain intensity scores, predicts 6-month levels of pain catastrophizing following hepatic resection: A trajectory analysis.

Eur J Pain 2019 03 8;23(3):503-514. Epub 2018 Nov 8.

Department of Anaesthesia and Pain Management, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Background: The study aims were to model acute pain intensity and opioid consumption trajectories up to 72 hr after open hepatic resection, identify predictors of trajectory membership and examine the association between trajectory memberships and 6-month pain and psychological outcomes. This is a long-term analysis of a published randomized controlled trial on the impact of medial open transversus abdominis plane catheters on post-operative outcomes.

Methods: A total of 152 patients (89 males; mean age 63.0 [range: 54-72]) completed questionnaires on pain and related characteristics pre-operatively and 6 months post-operatively. Total opioid use was recorded several times over a 72-hr period while self-reported pain intensity scores were collected multiple times until hospital discharge. Analyses were carried out using growth mixture modelling, logistic regression and general linear models.

Results: Both pain intensity and opioid consumption showed that a four-trajectory model best fits the data. Patients in the lowest opioid consumption trajectory were more likely to be classified in the constant mild pain intensity trajectory. Age and baseline levels of anxiety significantly predicted opioid trajectory membership while baseline depressive symptoms significantly predicted pain intensity trajectory membership. Patients in the two highest opioid consumption trajectories reported significantly higher levels of pain catastrophizing at 6 months compared to patients in the other 3 trajectories (all p < 0.05).

Conclusion: High consumption of opioids after surgery is associated with higher levels of pain catastrophizing 6 months later. Identification of patients within these trajectories may lead to the development of early interventions targeted to high risk individuals.

Significance: Differences in initial levels of opioid consumption and rates of change in opioid consumption shortly after surgery can help predict long-term psychological responses to pain. Identifying key characteristics associated with initial opioid consumption can lead to the development of cost-effective early interventions targeted to high risk individuals.
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http://dx.doi.org/10.1002/ejp.1324DOI Listing
March 2019

Splenectomy as Flow Modulation Strategy and Risk Factors of De Novo Portal Vein Thrombosis in Adult-to-Adult Living Donor Liver Transplantation.

Liver Transpl 2018 09;24(9):1209-1220

Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada.

Portal vein thrombosis (PVT) is a severe complication after liver transplantation that can result in increased morbidity and mortality. Few data are available regarding risk factors, classification, and treatment of PVT after living donor liver transplantation (LDLT). Between January 2004 and November 2014, 421 adult-to-adult LDLTs were performed at our institution, and they were included in the analysis. Perioperative characteristics and outcomes from patients with no-PVT (n = 393) were compared with those with de novo PVT (total portal vein thrombosis [t-PVT]; n = 28). Ten patients had early portal vein thrombosis (e-PVT) occurring within 1 month, and 18 patients had late portal vein thrombosis (l-PVT) appearing later than 1 month after LDLT. Analysis of perioperative variables determined that splenectomy was associated with t-PVT (hazard ratio [HR], 3.55; P = 0.01), e-PVT (HR, 4.96; P = 0.04), and l-PVT (HR, 3.84; P = 0.03). In contrast, donor age was only found as a risk factor for l-PVT (HR, 1.05; P = 0.01). Salvage rate for treatment in e-PVT and l-PVT was 100% and 50%, respectively, without having an early event of rethrombosis. Mortality within 30 days did not show a significant difference between groups (no-PVT, 2% versus e-PVT, 10%; P = 0.15). No significant differences were found regarding 1-year (89% versus 92%), 5-year (79% versus 82%), and 10-year (69% versus 79%) graft survival between the t-PVT and no-PVT groups, respectively (P = 0.24). The 1-year (89% versus 96%), 5-year (82% versus 86%), and 10-year (79% versus 83%) patient survival was similar for the patients in the no-PVT and t-PVT groups, respectively (P = 0.70). No cases of graft loss occurred as a direct consequence of PVT. In conclusion, the early diagnosis and management of PVT after LDLT can lead to acceptable early and longterm results without affecting patient and graft survival.
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http://dx.doi.org/10.1002/lt.25212DOI Listing
September 2018

In Situ Cold Perfusion of the Liver on Cardiopulmonary Bypass: Coagulopathy and Its Correction: A Case Report.

A A Pract 2018 Nov;11(10):263-267

From the Department of Anesthesia, University of Toronto and University Health Network, Toronto, Ontario, Canada.

We report a case of profound coagulopathy after the dual insult of cold in-situ perfusion of the liver and cardiopulmonary bypass in a patient undergoing complex hepatobiliary and cardiovascular surgery. Management of this coagulopathy with conventional blood products was hindered by elevated venous pressures, thought to contribute to persistent bleeding and risked liver and right ventricular dysfunction, necessitating a change in strategy. Anesthesiologists should consider fluid-restrictive strategies to correct coagulopathy in combined liver and cardiac surgery.
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http://dx.doi.org/10.1213/XAA.0000000000000802DOI Listing
November 2018

Liver Transplantation Without Venovenous Bypass: Does Surgical Approach Matter?

Transplant Direct 2018 May 24;4(5):e348. Epub 2018 Apr 24.

Multi-Organ Transplant Program, University of Toronto, Ontario, Canada.

Background: The use of venovenous bypass in liver transplantation has declined over time. Few studies have examined the impact of surgical approach in cases performed exclusively without venovenous bypass. We hypothesized that advances in liver transplant anesthesia and perioperative care have minimized the importance of surgical approach in the modern era.

Methods: Deceased donor liver transplants at the University of Toronto from 2000 to 2015 were reviewed, all performed without venovenous bypass. First, an unadjusted analysis was performed comparing perioperative outcomes and graft/patient survival for 3 different liver transplant techniques (caval interposition, piggyback, side-to-side cavo-cavostomy). Second, a propensity-matched analysis was performed comparing caval interposition to caval-preserving techniques.

Results: One thousand two hundred thirty-three liver transplants were included in the study. On unadjusted analysis, blood loss, transfusion requirement, postoperative complications, and graft/patient survival were equivalent for the 3 different techniques. To account for possible confounding patient variables, propensity matching was performed. Analysis of the propensity-matched cohorts also demonstrated similar outcomes for caval interposition versus caval-preserving approaches.

Conclusions: In the modern era at centers with a multidisciplinary team, the importance of specific liver transplant technique is minimized. Full or partial cross-clamping of the inferior vena cava is feasible without the use of venovenous bypass.
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http://dx.doi.org/10.1097/TXD.0000000000000776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959343PMC
May 2018

Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery.

N Engl J Med 2018 Jun 9;378(24):2263-2274. Epub 2018 May 9.

From Alfred Hospital (P.S.M., J.S., S.W.), Monash University (P.S.M., R.B., T.C., A.F., K.L., J.S., S.W.), and the University of Melbourne (R.B., P.P., D.S., C.C., K.L.), Melbourne, VIC, Austin Hospital, Heidelberg, VIC (R.B., P.P., D.S., C.C.), Royal Perth Hospital and the University of Western Australia, Perth (T.C.), Royal Melbourne Hospital, Parkville, VIC (K.L.), and Royal Adelaide Hospital and Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA (T.P.) - all in Australia; Auckland City Hospital, Auckland, and the Medical Research Institute of New Zealand, Wellington - both in New Zealand (S. McGuinness, R.P.); the Chinese University of Hong Kong, Hong Kong (M.T.V.C.); University Health Network, Toronto (S. McCluskey); and Derriford Hospital, Plymouth, United Kingdom (G.M.).

Background: Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion.

Methods: In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death.

Results: During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing.

Conclusions: Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury. (Funded by the Australian National Health and Medical Research Council and others; RELIEF ClinicalTrials.gov number, NCT01424150 .).
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http://dx.doi.org/10.1056/NEJMoa1801601DOI Listing
June 2018

Magnetic resonance guided focused high frequency ultrasound ablation for focal therapy in prostate cancer - phase 1 trial.

Eur Radiol 2018 Oct 25;28(10):4281-4287. Epub 2018 Apr 25.

Division of Urology, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada.

Objectives: To evaluate the feasibility and safety of focal therapy for low-intermediate risk prostate cancer (PCa) with magnetic resonance-guided high frequency focused ultrasound (MRgFUS) METHODS: This IRB-approved phase 1 prospective study enrolled eight patients with prostate specific antigen (PSA) ≤ 10 ng/ml, ≤ cT2a and Gleason score ≤ 7 (4 + 3) disease following informed consent. Under MRI guidance, focused high frequency ultrasound energy was delivered to ablate the target tissue. Treatment-related adverse events were recorded. Oncologic outcomes were evaluated with multiparametric MRI, PSA and TRUS biopsy at 6 months following treatment.

Results: Ten target lesions [six Gleason 6 lesions, two Gleason 7 (3 + 4) and two Gleason 7 (4 + 3)] were treated in eight men (prostate volume range, 25-50 cc; mean MRI time, 248 min per patient; mean sonication duration, 65 min). Mean target volume was 2.7 cc and mean post-treatment non-perfused volume was 4.3 cc. Quality of life parameters were similar between baseline and 6 months in 6/8 patients. All treated regions were negative on MRI; 4/8 patients and 6/10 target lesions (60%) were clear of disease on biopsy. One patient with 2-mm Gleason 8 disease in one of five cores from treatment site (4 + 3 disease at baseline) subsequently underwent prostatectomy with negative surgical margins. Three patients with low volume (5-15%) Gleason 6 residual disease were offered active surveillance. Mean PSA decreased from 5.06 at baseline to 3.4 ng/ml at 6 months.

Conclusion: MRgFUS is a feasible and safe method of noninvasively ablating low-intermediate risk PCa with acceptable short-term oncologic outcomes.

Key Points: • Focal therapy selectively ablates locally confined, clinically significant index lesion with a margin while sparing rest of gland and adjacent vital structures. • Magnetic resonance-guided focused high frequency ultrasound surgery (MRgFUS) combines MRI with HIFU. • MRgFUS provides ability to monitor treatments in real time and allows a targeted approach for focal ablation. • MRgFUS is a feasible, safe method of noninvasively ablating low-intermediate risk PCa. • MRgFUS provides acceptable oncologic outcomes at 6 months.
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http://dx.doi.org/10.1007/s00330-018-5409-zDOI Listing
October 2018

Cardiac output-based fluid optimization for kidney transplant recipients: a proof-of-concept trial.

Can J Anaesth 2018 08 10;65(8):873-883. Epub 2018 Apr 10.

Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, 200 Elizabeth Street, Eaton North 3-405, Toronto, ON, M5G 2C4, Canada.

Purpose: Intravenous fluid management for deceased donor kidney transplantation is an important, modifiable risk factor for delayed graft function (DGF). The primary objective of this study was to determine if goal-directed fluid therapy using esophageal Doppler monitoring (EDM) to optimize stroke volume (SV) would alter the amount of fluid given.

Methods: This randomized, proof-of-concept trial enrolled 50 deceased donor renal transplant recipients. Data collected included patient characteristics, fluid administration, hemodynamics, and complications. The EDM was used to optimize SV in the EDM group. In the control group, fluid management followed the current standard of practice. The groups were compared for the primary outcome of total intraoperative fluid administered.

Results: There was no difference in the mean (standard deviation) volume of intraoperative fluid administered to the 24 control and 26 EDM patients [2,307 (750) mL vs 2,675 (842) mL, respectively; mean difference, 368 mL; 95% confidence interval (CI), - 87 to + 823; P = 0.11]. The incidence of complications in the control and EDM groups was similar (15/24 vs 17/26, respectively; P = 0.99), as was the incidence of delayed graft failure (8/24 vs 11/26, respectively; P = 0.36).

Conclusions: Goal-directed fluid therapy did not alter the volume of fluid administered or the incidence of complications. This proof-of-concept trial provides needed data for conducting a larger trial to determine the influence of fluid therapy on the incidence in DGF in deceased donor kidney transplantation.

Trial Registration: www.clinicaltrials.gov (NCT02512731). Registered 31 July 2015.
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http://dx.doi.org/10.1007/s12630-018-1118-yDOI Listing
August 2018

Expanding the donor pool: Donation after circulatory death and living liver donation do not compromise the results of liver transplantation.

Liver Transpl 2018 06 14;24(6):779-789. Epub 2018 May 14.

Department of Surgery, Toronto General Hospital, Onatrio, Canada.

Because of the shortfall between the number of patients listed for liver transplantation (LT) and the available grafts, strategies to expand the donor pool have been developed. Donation after circulatory death (DCD) and living donor (LD) grafts are not universally used because of the concerns of graft failure, biliary complications, and donor risks. In order to overcome the barriers for the implementation of using all 3 types of grafts, we compared outcomes after LT of DCD, LD, and donation after brain death (DBD) grafts. Patients who received a LD, DCD, or DBD liver graft at the University of Toronto were included. Between January 2009 through April 2017, 1054 patients received a LT at our center. Of these, 77 patients received a DCD graft (DCD group); 271 received a LD graft (LD group); and 706 received a DBD graft (DBD group). Overall biliary complications were higher in the LD group (11.8%) compared with the DCD group (5.2%) and the DBD group (4.8%; P < 0.001). The 1-, 3-, and 5-year graft survival rates were similar between the groups with 88.3%, 83.2%, and 69.2% in the DCD group versus 92.6%, 85.4%, and 84.7% in the LD group versus 90.2%, 84.2%, and 79.9% in the DBD group (P = 0.24). Furthermore, the 1-, 3-, and 5-year patient survival was comparable, with 92.2%, 85.4%, and 71.6% in the DCD group versus 95.2%, 88.8%, and 88.8% in the LD group versus 93.1%, 87.5%, and 83% in the DBD group (P = 0.14). Multivariate Cox regression analysis revealed that the type of graft did not impact graft survival. In conclusion, DCD, LD, and DBD grafts have similar longterm graft survival rates. Increasing the use of LD and DCD grafts may improve access to LT without affecting graft survival rates. Liver Transplantation 24 779-789 2018 AASLD.
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http://dx.doi.org/10.1002/lt.25068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099346PMC
June 2018

Surgical Complications after Right Hepatectomy for Live Liver Donation: Largest Single-Center Western World Experience.

Semin Liver Dis 2018 05 22;38(2):134-144. Epub 2018 Mar 22.

Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.

The authors assessed the incidence, management, and risk factors for postoperative complications after right lobe (RL) live donor hepatectomy in a high-volume center in North America. All donors undergoing an RL live donor hepatectomy between 2000 and 2017 at our institution were included. The primary outcome was the development of complications (both medical and surgical). Predictors of postoperative complications were determined by logistic regression. A total of 587 patients underwent RL live donor hepatectomy. Among those, 187 postoperative complications were diagnosed in 141 (24%) patients. One patient had >90-day morbidity, and there were no donor deaths. Overall complications were significantly higher in the first era, 2000 to 2008 (81 [57.4%]) versus the second era, 2009 to 2017 (60 [42.6%]) ( = 0.01). On multivariate analysis, the only predictor of postoperative complications was the center volume of RL live donor hepatectomy in the previous 12 months with an odds ratio of 0.97 (95% confidence interval: 0.95-0.99). In conclusion, increasing center volume is associated with lower rates of postoperative complications after RL living liver donation.
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http://dx.doi.org/10.1055/s-0038-1636932DOI Listing
May 2018

Postoperative ERAS Interventions Have the Greatest Impact on Optimal Recovery: Experience With Implementation of ERAS Across Multiple Hospitals.

Ann Surg 2018 06;267(6):992-997

Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Background: Enhanced recovery after surgery (ERAS) programs incorporate evidence-based practices to minimize perioperative stress, gut dysfunction, and promote early recovery. However, it is unknown which components have the greatest impact.

Objective: This study aims to determine which components of ERAS programs have the largest impact on recovery for patients undergoing colorectal surgery.

Methods: An iERAS program was implemented in 15 academic hospitals. Data were collected prospectively. Patients were considered compliant if >75% of the preoperative, intraoperative, and postoperative predefined interventions were adhered to. Optimal recovery was defined as discharge within 5 days of surgery with no major complications, no readmission to hospital, and no mortality. Multivariable analysis was used to model the impact of compliance and technique on optimal recovery.

Results: Overall, 2876 patients were enrolled. Colon resections were performed in 64.7% of patients and 52.9% had a laparoscopic procedure. Only 20.1% of patients were compliant with all phases of the pathway. The poorest compliance rate was for postoperative interventions (40.3%) which was independently associated with an increase in optimal recovery (RR = 2.12, 95% CI 1.81-2.47). Compliance with ERAS interventions remained associated with improved outcomes whether surgery was performed laparoscopically (RR = 1.55, 95% CI 1.23-1.96) or open (RR = 2.29, 95% CI 1.68-3.13). However, the impact of ERAS compliance was significantly greater in the open group (P < 0.001).

Conclusions: Postoperative compliance is the most difficult to achieve but is most strongly associated with optimal recovery. Although our data support that ERAS has more effect in patients undergoing open surgery, it also showed a significant impact on patients treated with a laparoscopic approach.
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http://dx.doi.org/10.1097/SLA.0000000000002632DOI Listing
June 2018
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