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.

Pasireotide for the Prevention of Pancreatic Fistula Following Pancreaticoduodenectomy: A Cost-effectiveness Analysis.

OBJECTIVE: To determine the cost-effectiveness of perioperative administration of pasireotide for reduction of pancreatic fistula (PF). SUMMARY: PF is a major complication following pancreaticoduodenectomy (PD), associated with significant morbidity and healthcare-related costs. Pasireotide is a novel multireceptor ligand somatostatin analogue, which has been demonstrated to reduce the incidence of PF following pancreas resection; however, the drug cost is significant. This study sought to estimate the cost-effectiveness of routine administration of pasireotide to patients undergoing PD, compared with no intervention from the perspective of the hospital system. METHODS: A decision-analytic model was developed to compare costs for perioperative administration of pasireotide versus no pasireotide. The model was populated using an institutional database containing all PDs performed 2002 to 2012 at a single institution, including data regarding clinically significant PF (International Study Group on Pancreatic Fistula Grade B or C) and hospital-related inpatient costs for 90 days following PD, converted to 2014 $USD. Relative risk of PF associated with pasireotide was estimated from the published literature. Deterministic and probabilistic sensitivity analyses were performed to test robustness of the model. RESULTS: Mean institutional cost of index admissions was $67,417 and $31,950 for patients with and without PF, respectively. Pasireotide was the dominant strategy, associated with savings of $1685, and a mean reduction of 1.5 days length of stay. Univariate sensitivity analyses demonstrated cost-savings down to a PF rate of 5.6%, up to a relative risk of PF of 0.775, and up to a drug cost of $2817. Probabilistic sensitivity analysis showed 79% of simulations were cost saving. CONCLUSIONS: Pasireotide appears to be a cost-saving treatment following PD across a wide variation of clinical and cost scenarios.

A decision model and cost analysis of intra-operative cell salvage during hepatic resection.

BACKGROUND: Intraoperative cell salvage (ICS) can reduce allogeneic transfusions but with notable direct costs. This study assessed whether routine use of ICS is cost minimizing in hepatectomy and defines a subpopulation of patients where ICS is most cost minimizing based on patient transfusion risk. METHODS: A decision model from a health systems perspective was developed to examine adoption and non-adoption of ICS use for hepatectomy. A prospectively maintained database of hepatectomy patients provided data to populate the model. Probabilistic sensitivity analysis was used to determine the probability of ICS being cost-minimizing at specified transfusion risks. One-way sensitivity analysis was used to identify factors most relevant to institutions considering adoption of ICS for hepatectomies. RESULTS: In the base case analysis (transfusion risk of 28.8%) the probability that routine utilization of ICS is cost-minimizing is 64%. The probability that ICS is cost-minimizing exceeds 50% if the patient transfusion risk exceeds 25%. The model was most sensitive to patient transfusion risk, variation in costs of allogeneic blood, and number of appropriate cases the device could be used for. CONCLUSIONS: ICS is cost-minimizing for routine use in liver resection, particularly when used for patients with a risk of transfusion of 25% or greater.

Costs and cost-effectiveness of pediatric inguinal hernia repair in Uganda.

BACKGROUND: Surgically treatable diseases contribute approximately 11% of disability-adjusted life years (DALYs) worldwide yet they remain a neglected public health priority in low- and middle-income countries (LMICs). Pediatric inguinal hernia is the most common congenital abnormality in newborns and a major cause of morbidity and mortality yet elective repair remains largely unavailable in LMICs. This study is aimed to determine the costs and cost-effectiveness of pediatric inguinal hernia repair (PIHR) in a low-resource setting. METHODS: Medical costs of consecutive elective PIHRs were recorded prospectively at two centers in Uganda. Decision modeling was used to compare two different treatment scenarios (adoption of PIHR and non-adoption) from a provider perspective. A Markov model was constructed to estimate health outcomes under each scenario. The robustness of the cost-effectiveness results in the base case analysis was tested in one-way and probabilistic sensitivity analysis. The primary outcome of interest was cost per DALY averted by the intervention. RESULTS: Sixty-nine PIHRs were performed in 65 children (mean age 3.6 years). Mean cost per procedure was $86.68 US (95% CI 83.1-90.2 USD) and averted an average of 5.7 DALYs each. Incremental cost-effectiveness ratio was $12.41 per DALY averted. The probability of cost-effectiveness was 95% at a cost-effectiveness threshold of $35 per averted DALY. Results were robust to sensitivity analysis under all considered scenarios. CONCLUSION: Elective PIHR is highly cost-effective for the treatment and prevention of complications of hernia disease even in low-resource settings. PIHR should be prioritized in LMICs alongside other cost-effective interventions.

Determination of factors predictive of outcome for patients undergoing a pancreaticoduodenectomy of pancreatic head ductal adenocarcinomas.

INTRODUCTION: A pancreaticoduodenectomy is the reference treatment for a resectable pancreatic head ductal adenocarcinoma. The probability of 5-year survival in patients undergoing such treatment is 5-25% and is associated with relatively high peri-operative morbidity and mortality. The objective of the present study was to evaluate risk factors predictive of outcome for patients undergoing a pancreaticoduodenectomy for a pancreatic adenocarcinoma. METHODS: This retrospective analysis incorporated data from the Vancouver General Hospital and the British Columbia Cancer Agency (BCCA) from 1999-2007. RESULTS: The 5-year survival of 100 patients was 12% with a median survival of 16.5 months. Ninety-day mortality was 7%. Predictors of 90-day mortality included age ≥ 80 years (P < 0.001) and an American Society of Anesthesiologists (ASA) score = 3 (P= 0.012) by univariate analysis and age ≥80 years (P < 0.001) by multivariate analysis. The identifiable predictive factor for poor 5-year survival was an ASA score = 3 (P= 0.043) whereas a Dindo-Clavien surgical complication grade ≥ 3 was associated with a worse outcome (P= 0.013). Referral to the BCCA was associated with a favourable 5-year survival (P= 0.001). CONCLUSIONS: The present study identifies risk factors for patient selection to enhance survival benefit in this patient population.

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.

Hemostasis and Hepatic Surgery.

Operative blood loss is a major source of morbidity and even mortality for patients undergoing hepatic resection. This review discusses strategies to minimize blood loss and the utilization of allogeneic blood transfusion pertaining to oncologic hepatic surgery.

Pediatric surgical camps as one model of global surgical partnership: a way forward.

BACKGROUND/PURPOSE: A uniquely Ugandan method of holding surgical "camps" has been one means to deal with the volume of patients needing surgery and provides opportunities for global partnership. METHODS: We describe an evolved partnership between pediatric surgeons in Uganda and Canada wherein Pediatric Surgical Camps were organized by the Ugandans with team participation from Canadians. The camp goals were to provide pediatric surgical and anesthetic service and education and to foster collaboration as a way forward to assist Ugandan health delivery. RESULTS: Three camps were held in Uganda in 2008, 2011, and 2013. A total of 677 children were served through a range of operations from hernia repair to more complex surgery. The educational mandate was achieved through the involvement of 10 Canadian trainees, 20 Ugandan trainees in surgery and anesthesia, and numerous medical students. Formal educational sessions were held. The collaborative mandate was manifest in relationship building, an understanding of Ugandan health care, research projects completed, agreement on future camps, and a proposal for a Canadian-Ugandan pediatric surgery teaching alliance. CONCLUSION: Pediatric Surgical Camps founded on global partnerships with goals of service, education, and collaboration can be one way forward to improve pediatric surgery access and expertise globally.

Outcomes of salvage surgery for epidermoid carcinoma of the anus following failed combined modality treatment.

BACKGROUND: Chemoradiation is first-line therapy for epidermoid carcinoma of the anus (ECA). Surgery is reserved for treatment failures. The authors report outcomes after salvage procedures for ECA. METHODS: All treatment failures managed with radical surgery between 1998 and 2006 in our institution were reviewed. The Kaplan-Meier method was used for survival analysis. Log-rank and Cox regression were used for univariate and multivariate analysis, respectively. RESULTS: Fifty-one patients underwent salvage abdominoperineal resection for locoregional failure. Five-year overall survival after abdominoperineal resection was 29% (median, 22 months). Age, gender, human immunodeficiency virus status, tumor-node-metastasis stage, node status, and failure type did not predict survival. Negative resection margin was most strongly associated with improved overall and disease-free survival (P = .03 and P < .0001, respectively). Median survival for patients undergoing inguinal lymph node dissection for regional recurrence (n = 6) was 11 months, with freedom from cancer achieved in 2 of 6 patients. CONCLUSIONS: Recurrent anal carcinoma after primary chemoradiotherapy carries a poor prognosis. Salvage abdominoperineal resection offers a potential for long-term survival.

Institutional practice and outcome variation in the management of congenital diaphragmatic hernia and gastroschisis in Canada: a report from the Canadian Pediatric Surgery Network.

BACKGROUND: Perinatal management of congenital diaphragmatic hernia (CDH) and gastroschisis (GS) remains nonstandardized and institution specific. This analysis describes practice and outcome variation across a national network. METHODS: A national, prospective, disease-specific database for CDH and GS was evaluated over 4 years. Centers were evaluated individually and defined as low (low-volume center [LVC]) or high (high-volume center [HVC]) volume based on case mean. RESULTS: Congenital diaphragmatic hernia. Two hundred fifteen liveborn cases were studied (mean, 14.3 cases/center) across 15 centers (8 LVCs and 7 HVCs). Significant interinstitutional practice variation was noted in rates of termination (0%-40%) and cesarean delivery (0%-61%). Centers demonstrated marked variation in ventilation strategies, vasodilator and paralytic use, timing of surgery, and rates of primary closure. Overall survival was 81.4% (LVC, 76.9%; HVC, 82.4%; P = .43). Gastroschisis. Four hundred sixteen cases were investigated (mean, 26 cases/center; range, 6-72) across 16 centers (10 LVCs and 6 HVCs). Cesarean delivery rates varied widely between centers (0%-86%) as did timing of closure (early vs delayed, 1%-100%). There was no difference in length of stay, days on total parenteral nutrition, and overall survival (94.3% vs 97.2%; P = .17) between LVCs and HVCs. CONCLUSIONS: The existence of perinatal practice and outcome variation for GS and CDH suggests targets for improved delivery of care and justifies efforts to standardize treatment on a national basis.

Adhesive small bowel obstruction in children: should we still operate?

PURPOSE: Adhesive small bowel obstruction (ASBO) is a significant cause of postoperative morbidity, yet studies characterizing outcomes in children are limited. Our aim was to review our experience to describe the role of operative and nonoperative therapy, markers of outcome, and burden of disease in children. MATERIALS AND METHODS: Admissions for ASBO at British Columbia Children's Hospital (Vancouver, British Columbia, Canada) identified by International Classification of Disease, Ninth Revision, codes were reviewed over a 10-year period. Demographic, clinical, laboratory, and operative details were collected for all patients. RESULTS: Our study identified 165 admissions of which 32 (19%) were managed with immediate operation, whereas 133 were initially managed nonoperatively. One hundred seven patients went on to laparotomy, whereas 26 (16%) were managed nonoperatively. Absence of leukocytosis and older age appeared to be associated with successful nonoperative therapy. Tachycardia and younger age appeared to be independent risk factors for failure of nonoperative management. Delayed surgery or conservative management did not cause an increase in complications. Appendectomy, stoma formation and closure, Nissen fundoplication, and Ladd's procedures were the most common procedures leading to ASBO. CONCLUSIONS: Conservative therapy is the preferred approach in selected patients with ASBO. However, 84% eventually require surgery. This differs markedly from results in adults where most resolve nonoperatively. Younger patients were more likely to fail conservative trials and were more likely to develop advanced disease, pointing to ASBO as a distinct disease entity in children.