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.

Laparoscopic versus open hepatic resection in patients ≥75 years old: A NSQIP analysis evaluating 2674 patients.

BACKGROUND: Previous studies report promising outcomes with minimally invasive (MIS) hepatectomy in elderly patients but remain limited by small size. This study aims to comparatively evaluate the demographics and outcomes of geriatric patients undergoing MIS and open hepatectomy. METHOD: The 2016-2021 NSQIP database was evaluated comparing patients ≥75 undergoing MIS versus open hepatectomy. Patient selection and outcomes were compared using bivariate analysis with multivariable modeling (MVR) evaluating factors associated with serious complications and mortality. Propensity score matched (PSM) analysis further evaluated serious complications, mortality, length of stay (LOS), Clavien Dindo Classification (CDC), and Comprehensive Complication Index (CCI) for cohorts. RESULTS: We evaluated 2674 patients with 681 (25.5%) receiving MIS hepatectomy. MIS approaches were used more for partial lobectomy (85.9% vs. 61.7%; p < 0.001), and required fewer biliary reconstructions (1.6% vs. 10.6%; p < 0.001). Patients were similar with regards to sex, body mass index, and other comorbidities. Unadjusted analysis demonstrated that MIS approaches had fewer serious complications (8.8% vs. 18.7%; p < 0.001). However, after controlling for cohort differences the MIS approach was not associated with reduced likelihood of serious complications (odds ratio [OR]: 0.77; p = 0.219) or mortality (OR: 1.19; p = 0.623). PSM analysis further supported no difference in serious complications (p = 0.403) or mortality (p = 0.446). However, following PSM a significant reduction in LOS (-1.99 days; p < 0.001), CDC (-0.26 points; p = 0.016) and CCI (-2.79 points; p = 0.022) was demonstrated with MIS approaches. CONCLUSIONS: This is the largest study comparing MIS and open hepatectomy in elderly patients. Results temper previously reported outcomes but support reduced LOS and complications with MIS approaches.

The utility of self-expanding metal stents in benign biliary strictures- a retrospective case series.

BACKGROUND: Benign biliary strictures can have a significant negative impact on patient quality of life. There are several modalities which can be utilized with the goal of stricture resolution. These techniques include balloon dilatation, placement of multiple plastic stents and more recently, the use of metal stents. The aim of this study was to evaluate the local success of self-expanding metal stents in successfully resolving benign biliary strictures. METHODS: This was a single institution, retrospective case series. Patients included in our study were patients who underwent endoscopic retrograde cholangiopancreatography with placement of self expanding metal stents for benign biliary strictures at our institution between 2016-2022. Patients were excluded for the following: malignant stricture, and inability to successfully place metal stent. Data was evaluated using two-sided t-test with 95% confidence interval. RESULTS: A total of 31 patients underwent placement of 43 self-expanding metal stents and met inclusion criteria. Mean age of patients was 59 ± 10 years, and were largely male (74.2% vs. 25.8%). Most strictures were anastomotic stricture post liver transplant (87.1%), while the remainder were secondary to chronic pancreatitis (12.9%). Complications of stent placement included cholangitis (18.6%), pancreatitis (2.3%), stent migration (20.9%), and inability to retrieve stent (4.7%). There was successful stricture resolution in 73.5% of patients with anastomotic stricture and 33.3% of patients with stricture secondary to pancreatitis. Resolution was more likely if stent duration was > / = 180 days (73.3% vs. 44.4%, p < 0.05). There was no demonstrated added benefit when stent duration was > / = 365 days (75% vs. 60.9%, p = 0.64). CONCLUSIONS: This study demonstrates that self expanding metal stents are a safe and effective treatment for benign biliary strictures, with outcomes comparable to plastic stents with fewer interventions. This study indicates that the optimal duration to allow for stricture resolution is 180-365 days.

Immunoglobulin gene conversion: synthesizing antibody diversification and DNA repair.

Recent developments in the field of antibody (Ab) diversification have rapidly advanced our understanding of the molecular mechanism underlying these events. Key to these developments was the identification of activation-induced cytidine deaminase (AID) as the central regulator of secondary Ab diversification, and the elucidation of its primary function as a DNA deaminase. Incredibly, current literature suggests the existence of a shared pathway, common to all secondary diversification processes, from which the separate outcomes branch outwards at various points. Immunoglobulin gene conversion (IGC) is one of these mechanisms and is used by a number of vertebrate species in both the development of the pre-immune repertoire and in affinity maturation. In a manner similar to other Ab diversification mechanisms, IGC has managed to co-opt a normal DNA repair pathway for the generation of receptor diversity. In the case of IGC specifically, that pathway is homologous recombination (HR). A burgeoning wealth of genetic, biochemical and structural data has clarified the roles of many key HR factors, allowing new insight into its molecular mechanism. These insights, combined with those from the common mechanism of AID action, synergize to develop an emerging picture of the mechanism underlying IGC.

NHEJ-deficient DT40 cells have increased levels of immunoglobulin gene conversion: evidence for a double strand break intermediate.

Activation-induced cytidine deaminase (AID) likely initiates immunoglobulin gene-conversion (GC) by deaminating cytidines within the V-region of chicken B-cells. However, the intervening DNA lesion required to initiate GC remains elusive. GC could be initiated by a single strand break or a double strand break (DSB). To distinguish between these possibilities, we examined GC in the chicken DT40 B cell line deficient in non-homologous end joining (NHEJ). It is known that the NHEJ and homologous recombination DNA repair pathways compete for DSBs. In light of this, if a DSB is the major intermediate, deficiency in NHEJ should result in increased levels of GC. Here we show that DNA-PKcs(-/-/-) and Ku70(-/-) DT40 cells had 5- to 10-fold higher levels of GC relative to wildtype DT40 as measured by surface IgM reversion and sequencing of the V-region. These data suggest that a DSB is the major DNA lesion that initiates GC.