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Pancreatic cancer patients have a high risk of venous thromboembolism (VTE). Plasminogen activator inhibitor 1 (PAI-1) inhibits plasminogen activators and increases the risk of thrombosis. PAI-1 is expressed by pancreatic tumors and human pancreatic cell lines. However, to date, there are no studies analyzing the association of active PAI-1 and VTE in pancreatic cancer patients. We investigated the association of active PAI-1 in plasma and VTE in pancreatic cancer patients. In addition, we determined if the presence of human pancreatic tumors expressing PAI-1 impairs venous thrombus resolution in mice. Plasma levels of active PAI-1 in patients with pancreatic cancer and mice bearing human tumors were determined by enzyme-linked immunosorbent assay. We measured PAI-1 expression in 5 different human pancreatic cancer cell lines and found that PANC-1 cells expressed the highest level. PANC-1 tumors were grown in nude mice. Venous thrombosis was induced by complete ligation of the inferior vena cava (IVC). Levels of active PAI-1 were independently associated with increased risk of VTE in patients with pancreatic cancer (subdistribution hazard ratio per doubling of levels: 1.39 [95% confidence interval, 1.09-1.78], P = .007). Mice bearing PANC-1 tumors had increased levels of both active human and active mouse PAI-1 and decreased levels of plasmin activity. Importantly, mice bearing PANC-1 tumors exhibited impaired venous thrombus resolution 8 days after IVC stasis compared with nontumor controls. Our results suggest that PAI-1 contributes to VTE in pancreatic cancer.

Background Some clinical studies have shown that low‐molecular‐weight heparins (LMWHs) prolong the survival of cancer patients. In addition, various anticoagulants have been shown to reduce growth of tumors in mice. However, there are no studies on the effect of the factor Xa inhibitor rivaroxaban on growth of human pancreatic tumors in nude mice. Objectives To test the hypothesis that the factor Xa inhibitor rivaroxaban reduces the growth of tissue factor (TF)‐positive pancreatic tumors but not TF‐negative pancreatic tumors in mice. Methods The TF‐positive human pancreatic cancer cell line BxPc‐3 and the TF‐negative human pancreatic cancer cell line MIA PaCa‐2 were injected subcutaneously into nude mice and tumors grown to a mean volume of ~100 mm3. Mice were then divided into two groups. One group was fed chow containing rivaroxaban (0.5 g/kg chow) whereas the other group was fed chow without rivaroxaban. Results Rivaroxaban significantly prolonged prothrombin time in tumor‐bearing mice. Rivaroxaban did not affect cell proliferation or growth of either BxPc‐3 or MIA PaCa‐2 tumors grown subcutaneously in nude mice. Conclusion Our results indicate that inhibition of factor Xa with rivaroxaban does not affect the growth of two human pancreatic tumors in nude mice.

HCT co-morbidity index (HCT-CI) is a valid predictor of TRM and OS, however it has not been tested with other HCT outcomes. KPS has a more subjective definition but also shows functional impairment is independently associated with shorter OS post HCT. We tested HCT-CI, KPS and the results of a comprehensive physical performance assessment pre-HCT with day+100 TRM, OS and novel outcomes of LOS, death during HCT admission, readmission and need for rehabilitation placement after discharge. 349 consecutive adult (≥18 years) patients had a first allogeneic HCT at a single center 2010-2016 and underwent a required physical performance assessment by 1 of 2 dedicated physical therapists within 4 weeks pre-HCT. Testing included: 25 step-ups on each side, unassisted sit to stands from an 18″ chair in 30 seconds, weight bearing ability, need for assistance with ambulation, motor strength in 4 extremities, sensory or coordination impairment, self-reported pain and time to recovery of cardiovascular parameters (heart rate, O2 saturation) to pre-exercise levels. We studied these variables and patient, disease and HCT variables on LOS and death during transplant admission, in addition to day+100 TRM and OS. LOS was defined as duration of hospitalization from inpatient admission including conditioning regimen and hematopoietic cell infusion to first post-HCT discharge. Death during HCT admission included any death during first hospitalization regardless of time post-HCT. Age, gender, race, disease, and conditioning regimen were not associated with any novel outcomes. LOS and/or death during HCT admission were significantly associated with donor relation, disease status, KPS, HCT-CI and age adjusted HCT-CI (AA-HCT-CI) ( Table 1). OS was associated with age, KPS, HCT-CI, and AA-HCT-CI. Presence of any self-reported pain or endurance limitations were significantly associated with lower OS (Figure 1). Endurance limitations were significantly associated with LOS and death during HCT admission (Table 1). Recovery of heart rate and O2 saturation to baseline within 3 minutes of exercise were significantly associated with LOS and death during HCT admission, respectively. Inability to perform >10 sit to stands in 30 seconds ( Figure 1) and needing assistance with ambulation were also significantly associated with lower OS. Limitations on endurance tests remained significantly associated with OS even when stratified by AA-HCT-CI risk group. Analyses are ongoing of readmissions and discharge to a rehabilitation facility. A comprehensive assessment of functional status and endurance pre-HCT can provide valuable insight into short and long-term post HCT outcomes. A formal physical performance assessment, in addition to KPS and HCT-CI, provides a robust evaluation of endurance and physical reserve that can potentially improve the pre-HCT selection process and prognostication.

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