Pancreatectomy Induces Cancer-Promoting Neutrophil Extracellular Traps.

BACKGROUND: Neutrophil extracellular traps (NETs) occur when neutrophil chromatin is decondensed and extruded into the extracellular space in a web-like structure. Originally described as an anti-microbial function, this process has been implicated in the pathogenesis of pancreatic disease. In addition, NETs are upregulated during physiologic wound-healing and coagulation. This study evaluated how the inflammatory response to pancreatic surgery influences NET formation. METHODS: For this study, 126 patients undergoing pancreatectomy gave consent before participation. Plasma was collected at several time points (preoperatively and through the postoperative outpatient visit). Plasma levels of NET markers, including cell-free DNA (cfDNA), citrullinated histone H3 (CitH3), interleukin (IL)-8, IL-6, and granulocyte colony-stimulating factor (G-CSF) were measured using enzyme-linked immunosorbent assay (ELISA). Patient clinical data were retrospectively collected from a prospectively maintained database. RESULTS: After pancreatic resection, NET markers (cfDNA and CitH3) were elevated, peaking on postoperative days 3 and 4. This increase in NETs was due to an inherent change in neutrophil biology. Postoperatively, NET-inducing cytokines (IL-8, IL-6, and G-CSF) were increased, peaking early in the postoperative course. The patients undergoing the robotic approach had a reduction in NETs during the postoperative period compared with those who underwent the open approach. The patients who experienced a pancreatic leak had an increase in NET markers during the postoperative period. CONCLUSIONS: Pancreatectomy induces cancer-promoting NET formation. The minimally invasive robotic approach may induce fewer NETs, although the current analysis was limited by selection bias. Pancreatic leak resulted in increased NETs. Further study into the potential for NET inhibition during the perioperative period is warranted.

Acute pancreatitis induces a transient hypercoagulable state in murine models.

BACKGROUND/OBJECTIVES: Although understudied, risk of venous thromboembolism (VTE) appears to be increased during acute pancreatitis (AP). We aimed to further characterize a hypercoagulable state associated with AP utilizing thromboelastography (TEG), a readily available, point of care test. METHODS: AP was induced in C57/Bl6 mice using l-arginine and caerulein. TEG was performed with citrated native samples. The maximum amplitude (MA) and coagulation index (CI), a composite marker of coagulability, were evaluated. Platelet aggregation was assessed using whole blood collagen-activated platelet impedance aggregometry. Circulating tissue factor (TF), the initiator of extrinsic coagulation, was measured with ELISA. A VTE model using IVC ligation followed by measurement of clot size and weight was evaluated. After IRB approval and consent, blood samples from patients hospitalized with a diagnosis of AP were evaluated by TEG. RESULTS: Mice with AP displayed a significant increase in MA and CI, consistent with hypercoagulability. Hypercoagulability peaked at 24 h after induction of pancreatitis, then returned to baseline by 72 h. AP resulted in significantly increased platelet aggregation and elevated circulating TF. Increased clot formation with AP was observed in an in vivo model of deep vein thrombosis. In a proof of concept, correlative study, over two thirds of patients with AP demonstrated an elevated MA and CI compared to the normal range, consistent with hypercoagulability. CONCLUSIONS: Murine acute pancreatitis results in a transient hypercoagulable state that can be assessed by TEG. Correlative evidence for hypercoagulability was also demonstrated in human pancreatitis. Further study to correlate coagulation measures to incidence of VTE in AP is warranted.

Biofilm Formation on Central Venous Catheters: A Pilot Study.

INTRODUCTION: Central line-associated bloodstream infection is a complication with serious consequences and biofilm development is thought to play a role. This study evaluated the impact of sterilization technique on central venous catheter (CVC) biofilm formation. MATERIALS AND METHODS: This pilot study was conducted in the surgical intensive care unit of a tertiary care facility. All CVCs were inserted with chlorhexidine preparation (CHG). CHG-only CVCs were compared to the use of CHG with chlorhexidine gluconate-impregnated sponge (CHGIS). After removal, a punch biopsy of the CVC was taken at the noted skin level. Scanning electron microscopy identified the stage of biofilm. Confocal laser scanning microscopy with SYPRO stain confirmed the presence of glycocalyx and a volumetric analysis was completed. RESULTS: Twenty four CVCs were collected. Indications for line placement were similar, with 42% placed for sepsis in the CHGIS group and 33% in the CHG group. There were no positive line cultures or bacteremia and 2/12 CHGIS patients had candidemia. CHGIS lines were in place for a mean of 91 h, compared to 60 h with CHG alone (P = 0.19). The interior of CVCs had lower stage biofilms than the exterior and lacked stage 4 biofilms. Stage 4 biofilms were present externally on 50% of CVCs (8/12 CHG and 4/12 CHGIS). Stage 3 biofilms were present on 7/12 CHG and 6/12 CHGIS interior samples. Volume analysis found an increase in biofilm and glycocalyx in CHGIS compared to CHG samples. CONCLUSIONS: This study identified biofilms on both surfaces of CVCs. No significant difference in biofilm formation was found based on a sterilization technique.

Implementing a robotic hepatopancreatobiliary program for new faculty: safety, feasibility and lessons learned.

Robotic surgery is increasingly utilized in hepatopancreatobiliary (HPB) surgery, but the learning curve is a substantial obstacle hindering implementation. Comprehensive robotic training can help to surmount this obstacle; however, despite the expansion of robotic training into residency and fellowship programs, limited data are available about how this translates into successful incorporation in faculty practice. All operations performed during the first three years of practice of a surgical oncologist at a tertiary care academic institution were retrospectively reviewed. The surgeon underwent comprehensive robotic training during residency and fellowship. 137 HPB operations were performed during the initial three years of practice. Over 80% were performed robotically each year across a spectrum of HPB procedures with a 6% conversion rate. Median operative time, a metric for operative proficiency and evaluation for a learning curve, was similar throughout the study period for each major operation and below several reported optimized operative time benchmarks. The major complications, defined as a Clavien-Dindo of 3 or more, were similar across the experience and comparable to published series. Comprehensive robotic training in residency and fellowship as well as a dedicated, well-trained operative team allows for early attainment of optimized outcomes in a new HPB robotic practice.

Implementing a Robotic Hepatopancreatobiliary Program for New Faculty: Safety, Feasibility and Lessons Learned.

Background: Robotic surgery is increasingly utilized in hepatopancreatobiliary (HPB) surgery, but the learning curve is a substantial obstacle hindering implementation. Comprehensive robotic training can help to surmount this obstacle; however, despite the expansion of robotic training into residency and fellowship programs, limited data is available about how this translates into successful incorporation in faculty practice. Methods: All operations performed during the first three years of practice of a complex general surgical oncology-trained surgical oncologist at a tertiary care academic institution were retrospectively reviewed. The surgeon underwent comprehensive robotic training during residency and fellowship. Results: 137 HPB operations were performed during the initial three years of practice. Over 80% were performed robotically each year across a spectrum of HPB procedures with a 6% conversion rate. Median operative time, the optimal metric for operative proficiency and evaluation for a learning curve, was similar throughout the study period for each major operation and below several reported optimized operative times. Major complications were similar across the experience and comparable to published series. Conclusion: Comprehensive robotic training in residency and fellowship as well as a dedicated, well-trained operative team allows for early attainment of optimized outcomes in a new HPB robotic practice.

Circulating Tumor DNA (ctDNA) Clearance May Predict Treatment Response in Neoadjuvant Colorectal Cancer Management.

Background: Circulating tumor DNA (ctDNA) is extracellular DNA released by tumors and has been proposed as a marker of residual disease as well as a predictor of disease recurrence in the adjuvant setting. However, data are lacking on the utility of this biomarker in the neoadjuvant setting. Methods: We performed a retrospective study of stage III and IV colorectal cancer patients receiving neoadjuvant treatment at a single institution. Results: Seventeen patients converted from a positive pre-neoadjuvant ctDNA to a negative ctDNA prior to surgery. Five patients remained persistently positive despite systemic treatment. ctDNA conversion was found to be associated with a higher incidence of favorable treatment effect scores on final surgical pathology. There was no difference in recurrence-free survival in this small population. Furthermore, no added benefit was identified for patients receiving additional neoadjuvant therapy after the time of positive to negative ctDNA conversion. Conclusions: This study highlights the potential utility of ctDNA and the need for prospective trials in the neoadjuvant setting to monitor treatment response and guide decisions on treatment duration.

Biologic Functions of Hydroxychloroquine in Disease: From COVID-19 to Cancer.

Chloroquine (CQ) and Hydroxychloroquine (HCQ), initially utilized in the treatment of malaria, have now developed a long list of applications. Despite their clinical relevance, their mechanisms of action are not clearly defined. Major pathways by which these agents are proposed to function include alkalinization of lysosomes and endosomes, downregulation of C-X-C chemokine receptor type 4 (CXCR4) expression, high-mobility group box 1 protein (HMGB1) inhibition, alteration of intracellular calcium, and prevention of thrombus formation. However, there is conflicting data present in the literature. This is likely the result of the complex overlapping pathways between these mechanisms of action that have not previously been highlighted. In fact, prior research has focused on very specific portions of particular pathways without describing these in the context of the extensive CQ/HCQ literature. This review summarizes the detailed data regarding CQ/HCQ's mechanisms of action while also providing insight into the overarching themes. Furthermore, this review provides clinical context to the application of these diverse drugs including their role in malaria, autoimmune disorders, cardiovascular disease, thrombus formation, malignancies, and viral infections.

The Use of Whole Blood in Rural Trauma Leads to Decreased Resource Utilization.

BACKGROUND: Nearly 40% of trauma deaths result from uncontrolled hemorrhage. Most of these deaths occur within 24 hours, highlighting the importance of early resuscitation. Balanced component resuscitation has been shown to improve outcomes in hemorrhagic shock. However, hemostatic properties may then be decreased, leading to inadequate coagulopathy treatment or higher transfusion requirements. Data comparing the efficacy of component vs. whole blood (WB) resuscitation in early trauma is poor, particularly in the rural population. This study investigates WB use and resource utilization at a rural Level 1 trauma center. METHODS: A prospective cohort study with historical controls (HC) was performed using patients over age 17 presenting as the highest priority trauma. Two units of WB were available to patients with signs of hemorrhagic shock, with subsequent transfusions via massive transfusion protocol or thromboelastography guidance. Component utilization, time to hemorrhage control, complications, and transfer times were examined. RESULTS: Forty patients received WB vs. 153 HC. WB patients had lower complication rates (35% vs. 55.6%; P = .02), and a significant reduction in pRBC utilization in the emergency department (0 vs. 2; P < .0001) and throughout admission (2.0 vs. 4.0; P = .0003). All patients had prolonged transport times given the rural setting (1.42 hours HC vs. 2.03 hours WB; P = .002). DISCUSSION: Unlike most urban WB studies, this study occurred in a rural area with extended transportation times, when WB is inaccessible for patients. Despite this delay, WB patients demonstrated lower component utilization and complication rates. Further research is needed to characterize the impact of early WB access.