Tranexamic Acid in Patients Undergoing Liver Resection: The HeLiX Randomized Clinical Trial.

Importance: Tranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear. Objective: To determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection. Design, Setting, and Participants: Multicenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization. Interventions: Tranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia. Main Outcomes and Measures: The primary outcome was receipt of red blood cell transfusion within 7 days of surgery. Results: The primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, -2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08). Conclusions and Relevance: Among patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02261415.

Bridging the gap: assessing the integration of robotic-assisted surgery into Canadian surgical training programs.

SummaryThe adoption of robotic surgery has surged globally across multiple surgical specialties, but uptake in Canada has unfolded at a slower pace. Surgical educators and trainees in Canada face potential challenges related to sufficient exposure, experience, and competence in robotic surgical procedures. We conducted a cross-sectional national survey to gain insight into the perspectives of program directors overseeing general surgery residency and fellowship programs on the integration of robotic surgery into Canadian surgical training programs. Despite the presence of robotic surgery platforms at most academic and academic-affiliated hospitals, few trainees have exposure to any robotic surgery. Furthermore, a gap exists between the training provided in robotic surgery and its anticipated relevance to trainees upon graduation. Increased focus on the integration of robotic surgery within general surgical training in Canada is required to equip trainees for their careers.

Rectus sheath catheters reduce opiate use in pancreaticoduodenectomy: a pre- and postintervention cohort study.

BACKGROUND: Pancreaticoduodenectomy is the only curative option for patients with pancreatic cancer; however, pain remains a considerable problem postoperatively. With many centres moving away from using epidural analgesia, there is the need to evaluate alternative opiate sparing techniques for postoperative analgesia. We sought to determine if rectus sheath catheters (RSCs) had an opiate sparing and analgesic effect compared with standard care alone (opiate analgesia). METHODS: We conducted a retrospective pre- and postintervention cohort study of patients undergoing pancreaticoduodenectomy at a single tertiary academic hospital in Toronto, Canada, between April 2018 and December 2019. All patients undergoing a pancreaticoduodenectomy were eligible for inclusion. Among the 101 patients identified, 84 (61 control, 23 RSCs) were analyzed after exclusion criteria were applied (epidural analgesia, admission to intensive care intubated or reintubated within the first 96 hours). The pre-intervention group received a semi-standardized course of analgesics, including intravenous hydromorphone, acetaminophen, ketamine, with or without nonsteroidal anti-inflammatory, and with or without intravenous lidocaine; the latter 2 drugs were at the individual anesthesiologist and surgeon's preference. For the postintervention group, the same course of analgesics were used, with the addition of RSCs. These were inserted at the end of the operation, with a loading dose of ropivacaine administered and followed by a programmed intermittent bolus regime for 72-96 hours. The primary outcome measure was total postoperative opiate consumption (oral morphine equivalents). Secondary outcomes included pain scores (numeric rating scale) and treatment-related adverse effects. RESULTS: Opiate consumption (oral morphine equivalents) at 96 hours was significantly lower (median 188 mg, interquartile range [IQR] 112-228 v. 242.4 mg, IQR 166.8-352) with and without RSC, respectively (p = 0.01). The RSC group used significantly less opiates at each time point from 24 hours postoperatively, with no significant difference in pain scores between the groups and no significant catheter-related complications. CONCLUSION: The use of RSCs was associated with significant reductions in postoperative opiate consumption. Given the ease of placement and management, with minimal complications, RSCs should be incorporated into a course of postoperative multimodal analgesia. A large scale randomized controlled trial should be conducted to further investigate these findings.

Tranexamic acid versus placebo to reduce perioperative blood transfusion in patients undergoing liver resection: protocol for the haemorrhage during liver resection tranexamic acid (HeLiX) randomised controlled trial.

INTRODUCTION: Despite use of operative and non-operative interventions to reduce blood loss during liver resection, 20%-40% of patients receive a perioperative blood transfusion. Extensive intraoperative blood loss is a major risk factor for postoperative morbidity and mortality and receipt of blood transfusion is associated with serious risks including an association with long-term cancer recurrence and overall survival. In addition, blood products are scarce and associated with appreciable expense; decreasing blood transfusion requirements would therefore have health system benefits. Tranexamic acid (TXA), an antifibrinolytic, has been shown to reduce the probability of receiving a blood transfusion by one-third for patients undergoing cardiac or orthopaedic surgery. However, its applicability in liver resection has not been widely researched. METHODS AND ANALYSIS: This protocol describes a prospective, blinded, randomised controlled trial being conducted at 10 sites in Canada and 1 in the USA. 1230 eligible and consenting participants will be randomised to one of two parallel groups: experimental (2 g of intravenous TXA) or placebo (saline) administered intraoperatively. The primary endpoint is receipt of blood transfusion within 7 days of surgery. Secondary outcomes include blood loss, postoperative complications, quality of life and 5-year disease-free and overall survival. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics boards at participating centres and Health Canada (parent control number 177992) and is currently enrolling participants. All participants will provide written informed consent. Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT02261415.

PATCH-DP: a single-arm phase II trial of intra-operative application of HEMOPATCH™ to the pancreatic stump to prevent post-operative pancreatic fistula following distal pancreatectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is the most significant cause of morbidity following distal pancreatectomy. Hemopatch™ is a thin, bovine collagen-based hemostatic sealant. We hypothesized that application of Hemopatch™ to the pancreatic stump following distal pancreatectomy would decrease the incidence of clinically-significant POPF. METHODS: We conducted a prospective, single-arm, multicentre phase II study of application of Hemopatch™ to the pancreatic stump following distal pancreatectomy. The primary outcome was clinically-significant POPF within 90 days of surgery. A sample size of 52 patients was required to demonstrate a 50% relative reduction in Grade B/C POPF from a baseline incidence of 20%, with a type I error of 0.2 and power of 0.75. Secondary outcomes included incidence of POPF (all grades), 90-day mortality, 90-day morbidity, re-interventions, and length of stay. RESULTS: Adequate fixation Hemopatch™ to the pancreatic stump was successful in all cases. The rate of grade B/C POPF was 25% (95%CI: 14.0-39.0%). There was no significant difference in the incidence of grade B/C POPF compared to the historical baseline (p = 0.46). The 90-day incidence of Clavien-Dindo grade ≥3 complications was 26.9% (95%CI: 15.6-41.0%). CONCLUSION: The use of Hemopatch™ was not associated with a decreased incidence of clinically-significant POPF compared to historical rates. (NCT03410914).

Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study.

INTRODUCTION: Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM). Its effectiveness was demonstrated from a high volume center, with uncertainty regarding the feasibility and safety at other centers. Therefore, we sought to assess the safety and feasibility of HAIP for the management of uCRLM at other centers. METHODS: We conducted a multicenter retrospective cohort study of patients with uCRLM treated with HAIP from January 2003 to December 2017 at six North American centers initiating the HAIP program. Outcomes included the safety and feasibility of HAIP chemotherapy. RESULTS: We identified 154 patients with HAIP insertion and the median age of 54 (48-61) years. The burden of disease was >10 intra-hepatic metastatic foci in 59 (38.3%) patients. Patients received at least one cycle of systemic chemotherapy before HAIP insertion. Major complications occurred in 7 (4.6%) patients during their hospitalization and 13 (8.4%) patients developed biliary sclerosis during follow-up. A total of 148 patients (96.1%) received at least one-dose of HAIP chemotherapy with a median of 5 (4-7) cycles. 78 patients (56.5%) had a complete or partial response and 12 (7.8%) received a curative liver resection. CONCLUSION: HAIP programs can be safely and effectively initiated in previously inexperienced centers with good response.

The impact of tranexamic acid on administration of red blood cell transfusions for resection of colorectal liver metastases.

BACKGROUND: Red blood cell transfusions (RBCT) remain a concern for patients undergoing hepatectomy. The effect of tranexamic acid (TXA), an anti-fibrinolytic, on receipt of RBCT in colorectal liver metastases (CRLM) resection was examined. METHODS: Hepatectomies for CRLM over 2009-2014 were included. Primary outcome was 30-day receipt of RBCT. Secondary outcomes were 30-day major morbidity (Clavien-Dindo III-V) and 90-day mortality. Multivariable modelling examined the adjusted association between TXA and outcomes. RESULTS: Of 433 included patients, 146 (34%) received TXA. TXA patients were more likely to have inflow occlusion (41.8% vs. 23.1%; p < 0.01) and major hepatectomies (56.1% vs. 45.6%; p = 0.0193). TXA was independently associated with lower risk of RBCT (Relative risk (RR) 0.59; 95% confidence interval (95%CI): 0.42-0.85), but not with 30-day major morbidity (adjusted RR 1.02; 95%CI: 0.64-1.60) and 90-day mortality (univariable RR 0.99; 95%CI: 0.95-1.03). CONCLUSION: Intraoperative TXA was associated with a 41% reduction in risk of 30 -day receipt of RBCT after hepatectomy for CRLM. This finding is important to potentially improve healthcare resource allocation and patient outcomes. Pending further evidence, intraoperative TXA may be an effective method of reducing RBCT in hepatectomy for CRLM.