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.

Comprehensive Cost Implications of Commercially Available Noninvasive Colorectal Cancer Screening Modalities.

BACKGROUND: There is an increasing usage of noninvasive screening modalities for colorectal cancer (CRC), primarily the fecal immunochemical test (FIT) and multi-target stool DNA test (Cologuard [CG]). The aim of this study was to determine the comprehensive, long-term cost implications of these noninvasive screening modalities. STUDY DESIGN: Using a national insurer-based administrative dataset, patients screened for CRC from January 1, 2019 to December 31, 2019 were analyzed. A hierarchical logic system was used to determine the primary screening modality for each patient. The total annual costs in US dollars ($) were extrapolated using number of patients screened, costs per test, screening intervals, and costs incurred from false results. Patients within our tumor registry diagnosed with CRC were matched to their claims data, and cancer stage distribution was compared. RESULTS: Of 119,334 members who underwent noninvasive screening, 38.1% underwent screening with FIT and 40.0% with CG. The combined annual cost for these 2 screening modalities was $13.7 million. By transitioning to FIT alone for all noninvasive screening, the total annual cost would decrease to $7.9 million, resulting in a savings of approximately $5.8 million per year. Additionally, by combining data from the network cancer registry and insurer-based claims dataset, we were able to match 533 individuals who underwent screening and were later diagnosed with CRC. The rate of early-stage (stage 0 to II) disease was found to be similar between those screened with FIT and CG (59.5% FIT vs 63.2% CG; p = 0.77). CONCLUSIONS: The adoption of FIT as the primary noninvasive CRC screening method has the potential to generate significant cost savings, and therefore, carries significant value implications for a large population health system.

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.

Robot Assisted Distal Pancreatectomy with Celiac Axis Resection (DP-CAR) for Pancreatic Cancer: Surgical Planning and Technique.

Malignant pancreatic tumors involving the celiac artery can be resected with a distal pancreatectomy, splenectomy and celiac axis resection (DP-CAR), relying on collateral flow to the liver through the gastroduodenal artery (GDA). In the current manuscript, the technical conduct of robotic DP-CAR is outlined. The greater curve of the stomach is mobilized with care to avoid sacrificing the gastroepiploic vessels. The stomach and liver are retracted cephalad to facilitate dissection of the porta hepatis. The hepatic artery (HA) is dissected and encircled with a vessel loop. The gastroduodenal artery (GDA) is carefully preserved. The common HA is clamped and triphasic flow in the proper HA via the GDA is confirmed using intra-operative ultrasound. A retropancreatic tunnel is made over the superior mesenteric vein (SMV). The pancreas is divided with an endovascular stapler at the neck. The inferior mesenteric vein (IMV) and splenic vein are ligated. The HA is stapled proximal to the GDA. The entire specimen is retracted laterally with further dissection cephalad to expose the superior mesenteric artery (SMA). The SMA is then traced back to the aorta. The dissection continues cephalad along the aorta with the bipolar energy device used to divide the crural fibers and celiac nerve plexus. The specimen is mobilized from the patient's right to left until the origin of the celiac axis is identified and oriented towards the left. The trunk is circumferentially dissected and stapled. Additional dissection with hook cautery and the bipolar energy device fully mobilizes the pancreatic tail and spleen. The specimen is removed from the left lower quadrant extraction site and one drain is left in the resection bed. A final intra-operative ultrasound of the proper HA confirms pulsatile, triphasic flow in the artery and liver parenchyma. The stomach is inspected for evidence of ischemia. Robotic DP-CAR is safe, feasible and when used in conjunction with multi-modality therapy, offers potential for long-term survival in selected patients.

Formal robotic training diminishes the learning curve for robotic pancreatoduodenectomy: Implications for new programs in complex robotic surgery.

INTRODUCTION: The learning curve associated with robotic pancreatoduodenectomy (RPD) is a hurdle for new programs to achieve optimal results. Since early analysis, robotic training has recently expanded, and the RPD approach has been refined. The purpose of this study is to examine RPD outcomes for surgeons who implemented a new program after receiving formal RPD training to determine if such training reduces the learning curve. METHODS: Outcomes for consecutive patients undergoing RPD at a single tertiary institution were compared to optimal RPD benchmarks from a previously reported learning curve analysis. Two surgical oncologists with formal RPD training performed all operations with one surgeon as bedside assistant and the other at the console. RESULTS: Forty consecutive RPD operations were evaluated. Mean operative time was 354 ± 54 min, and blood loss was 300 ml. Length of stay was 7 days. Three patients (7.5%) underwent conversion to open. Pancreatic fistula affected five patients (12.5%). Operative time was stable over the study and lower than the reported benchmark. These RPD operative outcomes were similar to reported surgeon outcomes after the learning curve. CONCLUSION: This study suggests formal robotic training facilitates safe and efficient adoption of RPD for new programs, reducing or eliminating the learning curve.